review a review on the beneﬁcial aspects of food...

REVIEW

A review on the beneficial aspects of food processing

Martinus van Boekel1, Vincenzo Fogliano2, Nicoletta Pellegrini3, Catherine Stanton4,Gabriele Scholz5, Sam Lalljie6, Veronika Somoza7, Dietrich Knorr8, Pratima Rao Jasti9

and Gerhard Eisenbrand10

1 Wageningen University, Product Design & Quality Management Group, Wageningen, The Netherlands2 Dipartimento di Scienza degli Alimenti, Universita di Napoli ‘‘Federico II’’, Portici, Napoli, Italy3 Department of Public Health, University of Parma, Parma, Italy4 Teagasc, Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland5 Nestle Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland6 Unilever, Colworth House, Sharnbrook, Bedfordshire, UK7 Research Platform Molecular Food Science, University of Vienna, Vienna, Austria8 Berlin University of Food Technology, Berlin, Germany9 ILSI Europe a.i.s.b.l., Brussels, Belgium10 Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern,

Kaiserslautern, Germany

Received: December 22, 2009

Revised: June 7, 2010

Accepted: June 8, 2010

The manuscript reviews beneficial aspects of food processing with main focus on cooking/heat

treatment, including other food-processing techniques (e.g. fermentation). Benefits of thermal

processing include inactivation of food-borne pathogens, natural toxins or other detrimental

constituents, prolongation of shelf-life, improved digestibility and bioavailability of nutrients,

improved palatability, taste, texture and flavour and enhanced functional properties, including

augmented antioxidants and other defense reactivity or increased antimicrobial effectiveness.

Thermal processing can bring some unintentional undesired consequences, such as losses of

certain nutrients, formation of toxic compounds (acrylamide, furan or acrolein), or of compounds

with negative effects on flavour perception, texture or colour. Heat treatment of foods needs to be

optimized in order to promote beneficial effects and to counteract, to the best possible, undesired

effects. This may be achieved more effectively/sustainably by consistent fine-tuning of technolo-

gical processes rather than within ordinary household cooking conditions. The most important

identified points for further study are information on processed foods to be considered in epide-

miological work, databases should be built to estimate the intake of compounds from processed

foods, translation of in-vitro results to in-vivo relevance for human health should be worked on,

thermal and non-thermal processes should be optimized by application of kinetic principles.

Keywords:

Allergens / Antioxidants / Kinetics / Maillard reaction products / Polyphenols

1 Introduction

1.1 Reasons for the study

In a previous study, an Expert Group of the ILSI Europe

Process-Related Compounds Task Force focussed on risk-

benefit considerations of food processing and published a

paper: ‘Risk benefit considerations of mitigation measures

on acrylamide content of foods – a case study on potatoes

cereals and coffee’ [1]. This article serves as a useful tool for

risk assessors and risk managers to help in science-based

Commissioned by the ILSI Europe Process Related Compounds and

Natural Toxins Task Force.

Abbreviations: ACE, angiotensin I-converting enzyme; CGA,

chlorogenic acid; CI, confidence interval; CML, carboxymethyl-

lysine; CVD, cardiovascular disease; DM, diabetes mellitus; GST,

glutathione S-transferase; MRPs, maillard reaction products; RS,

resistant starch; TAC, total antioxidant capacity

Correspondence: Dr. Pratima Rao Jasti, ILSI Europe a.i.s.b.l.,

Avenue E. Mounier 83, Box 6-1200 Brussels, Belgium

E-mail: [email protected]

Fax: 132-2-762-00-44

& 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1215DOI 10.1002/mnfr.200900608

decision making, and it can be used as a basis for education

and communication to food processors and consumers.

In contrast to the adverse effects of processing and

cooking, the beneficial effects of processing received little

attention to date, but it is an important component in any

risk-benefit debate on the thermal or heat treatment of

foods. The previous study focussed on the risks rather than

the benefits of (thermal) food processing. Consequently, the

ILSI Europe Process-Related Compounds and Natural

Toxins Task Force held a brainstorming meeting and it was

decided to undertake a study on the beneficial aspects of

thermal food processing.

Thus, the ILSI Europe task force commissioned an

independent Expert Group to undertake this study to iden-

tify the beneficial changes to food that occur during thermal

treatment of foods, to ensure the safety and quality of food

while ensuring consumer acceptability as occurs during

industrial food processing and during household cooking.

The objective of this activity is to review the beneficial

aspects of cooking and food processing. Beneficial should be

understood as desirable in relation to health, to food safety,

to attractiveness of the food, to shelf-life and to sustain-

ability. This requires a holistic approach and aims at a

comprehensive description of beneficial aspects of cooking

and beneficial compounds involved. It will address the

current knowledge of compounds that may be formed

during the cooking process that may benefit to health. Gaps

in research will be identified. It is interesting to note that

most of the information related to health aspects of heat-

processed foods is on products such as coffee, cocoa, barley

in which the Maillard reaction plays an important role.

Food safety and palatability issues require the use of

thermal processes for modulation of food raw materials

during food processing at industrial and household levels.

Thermal treatment of foodstuffs induces several biological,

physical and chemical modifications, leading to sensory,

nutritional and textural changes. In general, the thermal

treatment of foods results in enhanced food safety and

quality.

Although some undesirable reactions are known to

occur, leading to loss of nutritional value and the formation

of potentially mutagenic and carcinogenic molecules, this

review will focus on the beneficial changes that occur during

processing of food. These include enhancement of nutri-

tional quality, release of bioactive and generation of bene-

ficial components, as well as destruction of negative activity

(anti-nutritional substances) that occur as a result of heat

treatments of food at household and industrial levels.

1.2 Anthropological aspects – historic aspects of

cooking and development of food processing

Foods have been heat-treated for many centuries, since our

ancestors learned, by trial and error, to master fire for

cooking purposes approx. 700 000 years ago, to modify and

preserve the organoleptic and nutritional properties of

foodstuffs. It is widely accepted by today’s anthropology that

the invention and continuous development of thermal food

treatment had a substantial, if not the major impact on

phenotypical, intellectual, societal and economic develop-

ment of mankind [2]. Since the late 19th century, the focus

began to change from home cooking to more industrialized

processes with initially an emphasis on preservation and

later on (1920–1930s) safety (microbial safety) and quality

issues, especially nutritional quality issues after the Second

World War.

Meanwhile new technologies became available, such

as steam and irradiation treatments to the use of micro-

waves. This has revolutionized the way home cooking is

nowadays done, with the availability and use of semi-

finished processed foods in everyday cooking. With the

availability of modern technology, it becomes possible to pay

more attention to gastronomic issues of foods. It is esti-

mated that 80–90% of foods used in home cooking are

semi-processed and therefore it makes sense to consider

the beneficial effects of processing on safety and quality of

food [3].

Food-processing methods started with heating in bottles

and cans, as developed by Appert and later on Pasteur to

modern sterilization techniques, such as ultra high

temperature and other non-thermal techniques, as will be

discussed in the next section. The fact that less time is spent

at home cooking as a result of food processing has resulted

in a change in lifestyle and has also affected the health

status of the population (longer life expectancy) as a result of

the availability of consistently high quality, safe and nutri-

tious food. Thermal processing may lead to the formation of

compounds in food that warrant a critical review in terms of

their impact on health.

1.3 Processing of foods – at household and

industrial levels

The application of heat during household cooking of food-

stuffs encompasses a variety of processes, such as boiling,

frying, steaming, baking, stewing and roasting, in tradi-

tional and microwave and steam ovens. Industrial thermal

treatment of foodstuffs includes many of the processes also

listed for household cooking. In addition, heat has been

used in traditional transformation processes other than

cooking, such as toasting, kilning, coffee roasting, drying

processes, canning, pasteurization and related technology

(ultra high temperature treatment) smoking and extrusion

cooking. It is important to note that these processes can be

controlled much better on industrial scale than on house-

hold level.

The quality of food, from the nutritional, microbial safety

point of view and sensory aspects depends on a range of

variables from farm to fork, including the quality of the raw

material, processing techniques, packaging and cooking.

1216 M. van Boekel et al. Mol. Nutr. Food Res. 2010, 54, 1215–1247


The main purpose of industrial food processing is to provide

safe and high-quality food as demanded by the consumer

[4, 5].

2 Factors in processing that impact food

The most important beneficial aspects can be summarized

as follows:

(i) Food safety (pathogens): The main benefit of food

processing is inactivation of food-borne pathogens, as

is normally required by Food Safety Legislation.

(ii) Food safety (other aspects): inactivation of natural

toxins and enzymes, prolongation of shelf-life.

(iii) Nutritional value: improved digestibility, bioavail-

ability of nutrients.

(iv) Sensory quality: taste, texture and flavour.

(v) Functional health benefits: e.g. probiotics, prebiotics,

Maillard reaction products (MRPs), flavonoids, other

food constituents and their reaction products.

(vi) Convenience: availability of ready-to-eat and semi-

prepared foods, e.g. microwavable frozen meals.

(vii) Cost: economy of scale.

(viii) Diversity: independence from the seasonal availability

of foods, and introduction of global food supply chain.

(ix) Quality of life: improved because less time required

for food supply and preparation.

The focus of this study is on the first five benefits using

the example of foods identified at the beginning of this

section.

The first and foremost beneficial effect of food processing

is the destruction of unwanted compounds and micro-

organisms. The minimal heat treatment in this respect is

pasteurization: this comprises a time–temperature combi-

nation that inactivates pathogenic bacteria such as Myco-bacterium tuberculosis, Salmonellae species, Staphylococcusaureus, among others. Provided that the food is properly

packed (i.e. no recontamination after processing) and stored

refrigerated, pasteurized food is generally safe from a

microbiological point of view. A more intense heat treat-

ment is sterilization in which not only vegetative cells but

also spores are inactivated. If properly packed and if

recontamination is prevented, such foods are completely

safe from a microbiological point of view and can be kept

indefinitely. Another beneficial effect is the inactivation of

anti-nutritional factors such as protease inhibitors (e.g.trypsin inhibitors in soy) and other natural toxins. However,

the quality of sterilized foods will diminish over time

because of chemical changes taking place in the food. The

second effect is the prolongation of shelf-life, which is

generally determined by microbial changes, biochemical

changes, chemical and physical changes. Although micro-

bial and enzymatic changes may be stopped by heat inacti-

vation, chemical and physical changes continue to occur in

foods, whether they are sterilized or not. This is the reason

why sterilized foods can still have a limited shelf-life because

chemical changes such as the Maillard reaction may lead to

undesired flavour compounds and discolouration. A third

beneficial effect of cooking is enhanced digestibility of food

and bioavailability of nutrients. For example, denatured

proteins are generally more digestible than proteins that are

not denatured, because digestive enzymes can more easily

hydrolyse unfolded molecules than folded ones. Also, gela-

tinization of starch makes possible its hydrolysis by amylase

enzymes. Destruction of cell walls in plant materials may

improve the bioavailability of compounds such as carote-

noids and polyphenols. A fourth effect is the formation of

desired compounds such as flavour compounds, anti-

oxidants and colouring agents and a prime example of this

is the Maillard reaction, which leads to the formation of

desired flavour and colour changes in many foods. The fifth

effect is related to specific effects of processing on health-

promoting compounds.

These five effects illustrate the positive aspects of food

processing and some of them will be elaborated below.

However, processing can also damage food quality, leading

to undesired consequences, such as:

(i) losses of certain (essential) nutrients due to chemical

reactions (e.g. vitamin C, available lysine),

(ii) formation of undesired compounds, e.g. acrylamide,

acrolein chloropropanediols and –esters, heterocyclic

amines, etc.,(iii) in some cases, formation of compounds that have a

negative effect on flavour perception (for instance,

sulphur compounds formed during heating of milk [6]),

(iv) loss of texture, discolouration, etc.

Hence, processes need to be optimized such that the

desired beneficial effects are promoted and the undesired

effects are counteracted as much as possible. This section

discusses some technological means to realize such opti-

mization.

2.1 Optimization through reaction kinetics

Quality changes of food, be it heat-processed or not, are due

to changes at the chemical, biochemical, physical and

microbial levels. For example, the nutritional value of a

product may change because of oxidation of a vitamin

(chemical reaction), the colour of a food may change

because of enzymatic conversion of polyphenols (biochem-

ical reaction), phase changes may occur in food (physical

reaction) and foods may spoil because of bacteria or moulds

(microbial reaction). If we want to steer such reactions in a

desired way, there are two things we need to know:

(i) understanding of the reaction taking place and (ii) the

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1217


speed at which the reaction takes place. Foods are unstable

from a thermodynamic point of view, which basically means

that spoilage cannot be prevented in principle. However,

what can be influenced is the speed at which spoilage

takes place. We need at least two relations, one is to express

the change in a quality attribute as a function of time, and

the other is about the dependence of that change on

conditions such as temperature and pressure. If we apply

heat, temperature dependence needs to be known, if high-

pressure technology is used, the pressure dependence of a

reaction has to be known, if we apply electric fields, the

dependence on electric field strength, etc. This is the domain

of kinetics. van Boekel has addressed this topic extensively

and we refer to this reference for further details [7].

2.2 Types of processes

2.2.1 Thermal processes

Traditionally, thermal processes have been used extensively

in food technology. Only fairly recently have other technol-

ogies emerged (see below). Thermal processes can be clas-

sified according to the intensity of heat treatment:

pasteurization (in the range 70–801C, sterilization (in the

range 110–1201C), and ultra-high-temperature treatment (in

the range 140–1601C). The reason why thermal treatment is

effective is that the speed of reactions is increased with

temperature. Chemical reactions always increase with

temperature; biochemical and microbial reactions also

increase with temperature, but above a certain temperature

enzymes and microorganisms become inactivated. Physical

reactions and radical reactions are usually not so tempera-

ture dependent.

Various reactions of importance for food quality have

different temperature sensitivity, and this we can exploit to

our benefit (Fig. 1). Such a plot can be constructed using the

kinetic equations given in, for instance, [7]. Note that this is

not an Arrhenius plot because the x-axis does not reflect the

inverse of absolute temperature. The important process

variables here are time and temperature, and food technol-

ogists can manipulate these variables to the foods benefit,

i.e. producing foods that have the highest quality possible.

Such plots show at a glance which time–temperature

combinations lead to a desired effect, and they can be

constructed with the aid of reaction kinetics. Basically, such

a concept can be applied to any quality change that is

considered of importance, but the parameters need to be

derived from experiments.

Just one example shows the possibilities of this approach;

it is on reduction of acrylamide while keeping the quality

attribute of a desired brown colour, taken from the work of

De Vleeschouwer et al. [8] on a potato-based model system.

It shows the time at which a level of 0.2 mM acrylamide (as

an example of an undesired compound) is reached in the

system and the time to obtain a colour level that corresponds

to a melanoidin level of 10 mM (melanoidins are the brown

pigments and are usually desired compounds) (Fig. 2).

Figure 2 shows that acrylamide formation is slightly

more temperature dependent than colour formation. This

implies that reducing temperature will reduce acrylamide

formation more than colour formation. Hence, by heating at

a lower temperature and a longer time, acrylamide forma-

tion can be reduced while maintaining the same colour.

This is, thus, one of the ways to mitigate acrylamide

formation. In passing, we note that although many articles

have been published on acrylamide formation, it is not so

Log(

time)

Temperature (°C)

UHT region

60 70 80 90 100 110 120 130 140 150

Chemical reaction

Spore inactivation

Bacteria orenzymeinactivation

Figure 1. Schematic picture showing how the time to achieve a

certain effect depends on the temperature of a chemical reaction

and microbial/biochemical inactivation (after van Boekel, [7]).

-1

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

4

100 120 140 160 180 200 220

T (°C)

ln(t

ime)

Figure 2. Temperature-time plot showing the formation of 0.2

mM acrylamide (& ) and 10 mM melanoidins (K) in heated

potato-based asparagine-glucose model system (extracted from

Figure 4 in De Vleeschouwer et al., 2008).



easy to find reliable kinetic data that can be used to optimize

processing.

Such knowledge is now actively applied in the food

industry to optimize quality of food, something that is

impossible to do in home cooking. An important aspect of this

is to also consider process design. Applying a heat treatment

can be done in various ways, by indirect heat exchange but

also in some cases by direct heat exchange by injecting steam

into a liquid product. The speed of heat transfer is then

important and aspects such as residence time distributions

and temperature distributions come into play. Obviously, it

should be avoided that some parts of the food receive a very

intense treatment, whereas other parts are under-processed.

Hence, equipment design (including hygienic design) is an

important aspect to take into consideration.

After processing, it is of utmost importance to use the

right packaging material to retain the highest quality level

during storage. In addition, modern techniques such as

modified atmosphere and controlled atmosphere packaging

offer excellent opportunities to extend shelf-life, and thereby

enhance the beneficial effects of processing.

2.3 Flavour and texture

Flavour and texture are very important desirable, key quality

attributes. However, these attributes are not easily translated

into measurable parameters that can be controlled in a

technological way. Sensory studies are needed for this and

outcomes are not easily translated into industrial scale

processes and technologies. Although many such processes

can be conducted at laboratory and even at pilot plant scale,

upscaling to industrial scale remains a major technological

challenge. Qualitatively, however, it is clear that processing

has large, usually desired, effects on flavour and texture.

Flavour compounds are formed predominantly in the

Maillard reaction, e.g. [9] as a result of heat processing, but

also other reactions contribute [10]. Another reaction of

great importance to food quality is oxidation; this is,

however, not a desired reaction as it leads to formation of

undesired flavour compounds [10], sometimes also called

off-flavours.

Texture is certainly influenced by processing. Basically, a

desired texture arises from (i) gel formation caused by

biopolymers, i.e. proteins and polysaccharides, (ii) from

closely packed systems and (iii) from cellular materials

[11, 12]. A term used in this respect is soft solids. Gels can be

formed because of heat processing, but also because of pH

changes and changes in ionic strength and as a result of

enzymatic action; examples include many dairy products and

meat products, jams and gellies. Closely packed systems are,

for instance, vegetable purees and concentrated emulsions;

these are obviously processed foods. Cellular mate-

rials comprise fruits and vegetables, and processing has large

effects on their behaviour because processing usually disrupts

cell walls to some extent. Texture is the result of many

complex interactions of components in the food matrix and

processing offers the opportunity to influence these interac-

tions in a desired way [12]. The topic is too vast to discuss in

much detail here; we refer to a recent review [13].

2.4 Non-thermal processes

Some of the non-thermal-processing techniques are still in

their infancy and in an exploratory phase of investigation.

The ones we consider here are those that have commercial

application in the food industry, namely high-pressure,

pulsed electric fields, membrane processing, dehydration

and freezing. Table 1 summarizes advantages and dis-

advantages of these non-thermal processes in comparison to

thermal processes. It should be noted that high pressure

alone does not inactivate spores, but a combination of mild

heat treatment under pressure may be effective (which

makes it partly a heat treatment again); research is ongoing

(e.g. [14, 15]). Pressure-dependent freezing point depression

of water to �201C at 200 MPa and the formation of different

ice crystal types under pressure leads to unique high pres-

sure–low temperature applications [16, 17].

Pressure induces protein denaturation and individual

starch granules, which can also, – pressure and temperature

dependent – lead to gelatinization [16]. It should be noted

that pressure-induced gels differ in physico-chemical pro-

perties from heat-induced ones, thus allowing via T and pcombinations to create a wide variety of different gel struc-

tures [18]. In addition, pressure supported protein–poly-

saccharide interactions have led to the creation of new food

textures [16]. Compared with thermal processing, less work

has been done for non-thermal processes in terms of inac-

tivation kinetics and reaction mechanisms of nutrients,

toxins, allergens, microbes and viruses. More data are

needed on mechanisms of spore inactivation and on enzyme

inactivation. Shelf-life studies of non-thermally treated

products are desirable.

2.5 Fermentation processes

Fermentation is a non-thermal process that can be exploited

to produce beneficial effects in foods. It is a process by

which foods and drinks undergo chemical changes caused

by enzymes produced from bacteria, microorganisms or

yeasts, and is one of the oldest known food preservation

techniques. The process involves the action of desirable

microorganisms or their enzymes on food ingredients

causing biochemical changes, leading to significant modi-

fication of the food product. During fermentation, the

carbohydrate energy source in food, such as lactose in milk

is converted to lactic acid, as occurs during production of

yogurt and cheese from milk, and pickles from fruits and

vegetables. Yeasts (typically of the species Saccharomyces)convert glucose to ethanol and carbon dioxide during bread

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1219


Tab

le1.

Ad

van

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van

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of

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van

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on

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om

men

tsR

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ce

Th

erm

al

pro

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es

Safe

tyQ

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tyN

utr

itio

nal

valu

ela

rgely

main

tain

ed

Fo

rmati

on

of

un

desi

red

com

po

un

ds

(e.g

.acr

yla

mid

e)

Past

eu

riza

tio

n:

60–7

01C

Ste

riliza

tio

n:

110–1

501C

Inact

ivati

on

of

cells

Inact

ivati

on

of

spo

res

Fo

rmati

on

of

desi

red

[7,

201]

Inact

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on

of

an

ti-n

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fact

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(e.g

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600

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Cell

dis

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1–5

kV/c

m1–1

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[202,

203]

[204]

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making, and in the production of alcoholic beverages.

Moulds are also used in certain fermentation, such as

production of blue cheese and soy sauces. One of the

achievements of the past 50 years is that fermentation

processes are now well-controlled and can be tailored to

produce desired compounds, based on the selection of

starter bacteria and understanding the fermentation process

and thus manipulation of conditions [19].

The benefits of fermentation are shelf-life extension,

enrichment of the nutritive value of the food, enhancing the

taste and digestibility of milk and indeed improved food

safety e.g. by low pH and elimination of antinutrients during

the fermentation process.

2.6 Beneficial compounds from fermentation

During fermentation, a range of secondary metabolites are

produced, some of which have been associated with health-

promoting properties, most notably B vitamins and bioactive

peptides released from food proteins through microbial action.

Peptides with inhibitory properties against angiotensin

I-converting enzyme (ACE) are known to have an anti-hyper-

tensive effect and have been isolated from enzymatic digests of

various food proteins, whereas other properties ascribed to

bioactive peptides include antimicrobial, opiate, cholesterol-

lowering, immuno-stimulatory and mineral-utilizing proper-

ties (for review, see [20]). It is thus not surprising that the

consumption of fermented foods has long been associated

with good health. Indeed, dating back to 76 A.D., the Roman

historian Plinio advocated the use of fermented milks for

treating gastrointestinal infections, whereas the French

pediatrician Tissier proposed in the early 1900s that bifido-

bacteria may be effective in preventing infection in infants.

2.7 Probiotics

Furthermore, around this time, Elie Metchnikoff found that

the consumption of fermented milks could reverse putre-

factive effects of the gut micro flora, leading to the devel-

opment of the probiotic concept. Probiotics are defined as

‘‘live microorganisms which when administered in adequate

amounts confer a health benefit on the host’’ (ftp://ftp.

fao.org/docrep/fao/009/a0512e/a0512e00.pdf) [21]. There is

accumulating clinical evidence that probiotic bacteria posi-

tively affect certain human health conditions, including

overcoming lactose intolerance, preventing various diarrheal

illnesses, allergic disorders, bacterial vaginosis and urinary

tract infections, respiratory infections, dental caries, necro-

tizing enterocolitis and certain aspects of inflammatory

bowel disease [22]. Although specific numbers are not

mentioned in the definition, high levels of viable micro-

organisms are recommended in probiotic foods for efficacy

[23], given that many of the clinical studies use daily doses

in excess of 109 cfu/day.Tab

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Mol. Nutr. Food Res. 2010, 54, 1215–1247 1221


For successful delivery in foods, probiotics must survive

food processing and storage during product manufacture,

maturation and shelf-life. Appropriate processes must be

applied to guarantee viability of the bacteria at the end of the

shelf-life of the product. Probiotic strains are generally of the

genera Lactobacillus and Bifidobacterium, and to a lesser

extent Pediococcus, Propionibacterium, Enterococcus, Bacillus,Streptococcus and Saccharomyces. Freeze-dried powders and

frozen concentrates of probiotic Lactobacillus and Bifido-bacterium spp. have been developed, whereas spray drying

has been applied to the dehydration of a limited number of

probiotic cultures including lactobacilli and bifidobacteria

(for review, see [24]).

During freeze drying, cells are first frozen at �1961C and

then dried by sublimation under high vacuum and while

good probiotic survival rates are typically achieved in freeze-

dried powders, inactivation does occur, and is mainly asso-

ciated with the freezing step. The lipid fraction of the cell

membrane is known to be a primary target area for damage

during drying, where lipid peroxidation may occur while the

secondary structures of RNA and DNA destabilize, resulting

in reduced efficacy of DNA replication, transcription and

translation. Consequently, approaches that minimize damage

to these cellular components during the desiccation of

probiotics will deliver optimum results (for review, see [25]).

For successful spray drying of probiotic cultures, selec-

tion of the particular probiotic strain and the outlet

temperature of the spray drier are critical factors. The

process results in exposure of the live bacteria to heat stress,

leading to viability losses. The cytoplasmic membrane is

among the most susceptible sites in bacterial cells to the

stresses associated with spray drying, while the cell wall,

DNA and RNA are also affected, leading to loss of metabolic

activity. Therefore, in order to minimize damage during

spray drying of probiotic cultures, approaches such as

optimization of the drying technology, selection of suitable

drying matrix for encapsulation and manipulating probiotic

bacteria by classical (microbiological) approaches have

proved effective. For example, studies have shown that

probiotic performance can be improved via the addition to

the media of thermoprotectants (such as skim milk powder,

whey protein, trehalose, betaine, adonitol, etc.) prior to

drying (for review, see [24, 25]). The generation of live

probiotic cultures in dried format thus presents challenges

in terms of retaining probiotic functionality during powder

manufacture and storage. Both freeze drying and spray

drying can be used for manufacture of probiotic powders on

a large scale; however, both approaches expose the cultures

to extreme environmental conditions. Methods of produc-

tion of dried probiotic powders should be such that viability

is maintained in the dried powders following manufacture,

and storage to ensure that an adequate number of bacteria

can be delivered in the final product.

Consequently, the processing conditions relating to the

development of foods containing probiotics in sufficient

numbers in a stable live form that can withstand the product

shelf-life need to be overcome. These requirements pose a

significant challenge from a technological standpoint, since

many probiotic bacteria, being of intestinal origin, are

sensitive to stresses such as heat, oxygen and acid exposure.

Manipulation of the processing conditions and use of

processing aids may lead to improved delivery of viable

probiotics in foods.

2.8 Food additives

Beneficial aspects of food processing can be reached in

many ways. One of these ways is by adding ingredients.

Food additives have a bad reputation among consumers.

Nevertheless, they are intentionally used to improve food

quality. It comprises the use of flavouring agents, thicken-

ing agents, emulsifiers and foam stabilizers. They are

generally used to improve the stability of processed foods.

We discuss here the use of enzymes, preserving agents and

vitamins in somewhat more detail.

2.8.1 Enzymes as processing aids

The basic mechanism behind the action of enzymes is that

they act as catalysts and thereby speed up chemical reactions

enormously without the need for temperature increase.

Enzymes can act on the major nutrients in foods, carbohy-

drates, proteins, fats, but also on other compounds such as

phenols, chlorophyll. A detailed overview of the use of

enzymes in food technology is given by Parkin [26]. A typical

recent new example is the use of asparaginase to remove

one of the precursors of acrylamide during processing of

potatoes and doughs. The effect of enzymes is to improve

either the properties of a food, or to help in processing. For

example, in the production of fruit and vegetable juices,

pectolytic enzymes can be used to break down pectin in cell

walls, thus facilitating and improving yields in the extraction

process.

2.8.2 Preserving agents

Preserving agents obviously help to preserve food, the

beneficial effect being that spoilage of foods is postponed. In

most cases, these agents limit or prevent the growth of

micro-organisms. This concerns agents such as benzoic

acid, sorbic acid, lactic acid and acetic acid. Part of their

action is to lower the pH such that micro-organisms cannot

grow, but there are also specific effects on micro-organisms,

for instance, they may damage the membrane of micro-

organisms. Other preserving agents, such as sulphite,

interfere with chemical reactions, or they inhibit enzymes.

Salts such as NaCl, nitrite and nitrate can be added as

preserving agents. A recent overview on food additives can

be found in Lindsay [27].



2.8.3 Vitamins, minerals and antioxidants

For nutritional reasons, one can add micro-nutrients to

foods. For instance, folic acid to bread, iodine to bread and

calcium to drinks. Such foods are nowadays classified as

functional foods, the beneficial effect being that specific

needs can be fulfilled, such as folic acid for pregnant

women, extra calcium to combat osteoporosis. The prime

concern here is that in order to be really beneficial, the

added compounds need to retain their activity in the food up

until the moment they are consumed. Folic acid may be

subjected to chemical reaction, added salts may react. An

example of the latter is the following. If a product like soy

milk is fortified with a calcium salt, it strongly depends on

which salt is actually used. Some calcium salts may crys-

tallize, so if, for instance, calcium carbonate would be used,

it will precipitate in the milk, form a sediment layer (a sort

of cement) and is thus not adsorbed. Hence, although the

product does contain added calcium, it is of no use. In cow’s

milk, such crystallization does not happen because of the

association of calcium phosphate with casein micelles. Such

micelles are not present in soy milk. To prevent such things

from happening, a thorough knowledge of the behaviour of

the added compound in conjunction with interactions in the

food matrix is needed.

Antioxidants are used to prevent oxidation of compounds

that are prone to reaction with oxygen, such as vitamins and

unsaturated fatty acids. Oxidation is typically a problem for

stored processed foods and the use of antioxidants, in

combination with suitable packaging materials is clearly

beneficial.

3 Effects of processing on bioactivecompounds in food

The previous section described how the use of specific tech-

nologies can result in beneficial effects. This section deals

with the chemical changes, the modification and formation of

compounds considered beneficial for human health in terms

of digestibility, bioavailability and antioxidant activity.

In the past, much attention was paid to compounds

formed by heat processing that have potential adverse effects

for human health (e.g. acrylamide, furan, 3-mono-

chloropropane-1,2-diol (3-MCPD) and trans fatty acids),

shedding a rather negative light on processed foods. These

compounds will not be detailed here, the scope of this article

being the potential health beneficial effects, in line with

other recent efforts to balance potential adverse against

beneficial effects (risk-benefit assessment) (http://europe.

ilsi.org/activities/ecprojects/BRAFO/) [1, 28].

New compounds are formed upon processing, or existing

components are transformed that may express biologically

beneficial activities. Table 2 summarizes examples of such

compounds linked to the processes used. In addition,

Table 3 summarizes the effects of processing on the

formation/destruction of compounds with potentially

adverse effects.

3.1 Starch, dietary fibre, protein and allergens

Processing strongly affects the digestibility of macro-

nutrients. Cooking starchy foods (legumes, cereals and

potatoes) results in starch gelatinization and increases

digestibility of starch, which has been very beneficial for

mankind because it allowed to markedly enhance the caloric

intake. Paradoxycally, in the present era of abundancy where

people take in too many calories, research is now focused on

resistant starch (RS) which is slowly hydrolysed by amylase

and reaches the lower gut where it is fermented by gut

microbiota. The differing rates of absorption between RS

and digestible starch influence their differential metabolic

responses. RS intake decreases postprandial glycemic and

insulinemic responses, lowers plasma cholesterol and

triglyceride concentrations, improves whole body insulin

sensitivity, increases satiety and reduces fat storage [29].

Processing parameters such as time/temperature of

cooking, water availability and storage conditions can be

used to modulate the amount and the nature of RS. This

opens up many opportunities for future developments,

especially for tailor-made starch derivatives with multiple

modifications and with the desired functional and nutri-

tional properties [30].

Despite common beliefs, dietary fibre structure can also

be significantly affected by processing. Dietary fibre is

defined as non-digestible carbohydrates and lignin that are

intrinsic and intact in edible parts of plants. A definition for

Dietary Fiber was adopted in June 2009 by the CAC based

on the recommendation for endorsement of the CODEX

Committee on Nutrition and Foods for Special Dietary Uses

(CCNFSDU) in November 2008. The definition listed three

categories of carbohydrate polymers which are not hydro-

lyzed by the endogenous enzymes in the small intestine of

humans [31]:

(i) Edible carbohydrate polymers naturally occurring in

the food as consumed,

(ii) Carbohydrate polymers, which have been obtained

from food raw material by physical, enzymatic or

chemical means and which have been shown to have a

physiological effect of benefit to health as demonstrated

by generally accepted scientific evidence to competent

authorities and

(iii) Synthetic carbohydrate polymers which have been

shown to have a physiological effect of benefit to health

as demonstrated by generally accepted scientific

evidence to competent authorities.

Dietary fibre has traditionally been categorized according to

its solubility. Soluble fibres include gums, pectins and inulin,

whereas cellulose and fibre in wheat bran are two examples of

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1223


insoluble fibres. Although the distinction between soluble and

insoluble fibre was thought to determine the physiological

effect of fibre, other properties may be of more importance.

Two of these include viscosity and fermentability. Heat treat-

ment in wet conditions usually determines the hydrolysis of

the fibre (the more severe the treatment the higher the

hydrolysis) (for review, see Nyman [32]).

Processing can modify the solubility of the fibre by

reducing its molecular weight, enzymatically [33, 34] or

mechanically, for example, during extrusion by applying

different shear forces [35, 36].

Also for proteins, a number of factors affect their diges-

tion and limit their absorption. Some proteins are resistant

to proteolytic enzymes and pass through the small intestine

relatively intact. The protein digestion rate influences the

amount of protein that is absorbed in the small intestine.

Processing has a double contrasting effect on protein

digestibility that has been summarized by Friedman [37, 38].

(i) Denaturation can facilitate proteolysis, thus increasing

digestibility. This is particularly the case for some

vegetable proteins, which are poorly accessible in

uncooked material.

(ii) Processing results in the formation of protein aggre-

gates that are less digestible than the unprocessed

protein. This is particularly the case for animal proteins

and for systems heated in the presence of carbohydrates

(formation of crosslinked proteins).

3.1.1 Allergens

Allergens are proteins and therefore subject to denaturation

upon processing steps such as heating and high pressure.

Whether denaturation (and/or subsequent reactions) leads

to changes of the epitopes (the region on a protein recog-

nized by an antibody) that influence potential allergenicity

strongly depends on the molecular properties of the allergen

concerned [39]. An important point to note is that

some allergens are able to refold from the denatured state

[40] when the cause of denaturation is removed (e.g. upon

cooling), but it remains to be investigated whether these

refolded proteins are still able to provoke allergic reactions.

Food processing may increase or decrease the intrinsic

allergenicity of a protein, but current data do not facilitate

the identification of specific variables that could be used to

reliably determine how processing will influence protein

allergenicity [41].

The allergens that occur in fruits and that are related to

birch pollen allergies (the PR10 protein family, [42]) have

molecular similarities and are in general not very heat

stable. Their denaturation temperature is somewhere

between 45 and 801C [40]. For instance, the allergen from

apple, Mal d1, is quite heat labile. Thus, people allergic to

apples are generally able to eat processed apples as in apple

cake or apple sauce. The allergen from soya, Gly m4, seems

to be more heat stable and has been found to cause allergies

when present in processed soy products [43]. Also the major

allergen in peanuts, Ara h1, is very heat stable [44]. The

allergen from Brazil nut, Ber e1, is so heat stable that it does

not denature during common food processing [45].

Processing may also lead to enhancement of allergenic

activity. This is documented for instance, for allergens

subjected to the Maillard reaction. The phenomenon has

been demonstrated quite a while ago already for b-lacto-

globulin, the major allergen in milk [46]. Since the ability of

sugars to cause glycation differs considerably, this implies

that the extent of increased allergenicity depends on the type

of sugar. Also, temperature has a strong effect on the

Maillard reaction, and hence it depends on the intensity of

heating how strong this allergenicity increase will be. It has

been shown that Maillard-modified peanut allergens bind

more effectively to IgE and are at the same time also more

resistant to gastric hydrolysis [47, 48]. Hence, roasting of

peanuts could lead to an increased allergic reaction, but it is

not completely sure whether an increased IgE binding is

causing an increase in allergenicity. Supposedly, high-

pressure processing will not lead to an increase in aller-

genicity if there is no additional heat treatment. Depending

on the extent of denaturation and the ability to refold after

the treatment, allergenicity may actually decrease, as shown

for celery allergens [49].

Table 2. Effects of processing on the presence/absence (formation/destruction) of compounds to which beneficial effects have beenattributed

Compounds Foods Process Effect Reference

Antioxidant MRPs Different foods Thermal treatment Increase amount [101]Catechins Cocoa Alkalinization Decrease [209]Proanthocyanidins Cocoa Fermentation Increase amount [210]Carotenoids Tomato Heating to dissociate carotenoid protein Increase amount [59, 60]Glucosinolates Broccoli Steam heating Increase amount [60, 82]Glucosinolates Broccoli Frying, boiling Decrease amount [60]Flavonoids Different vegetables Heating Increase amount [60, 89, 90–94]Anthocyanins Fruits juice High pressure Avoid degradation [211]Organosulphur compounds Garlic onions Thermal treatment Decrease amount [212]Ascorbic acid Fruits and vegetables Thermal treatment Decrease amount [56]



A very effective way of reducing or removing allergenicity

is enzymatic hydrolysis, destroying the responsible epitopes.

By this way, hypo-allergenic foods (especially milk products)

can be developed. The downside of this treatment is, of

course, that the properties of the resulting food are drasti-

cally different from the original food. The treatment notably

affects texture and taste, as well as appearance. The resis-

tance to enzymatic hydrolysis is, incidentally, also of

importance for the occurrence of allergic reactions upon

digestion [50].

Other treatments such as g-irradiation, pulsed electric

fields and acoustic shocks, are not expected to have much

effect on allergens, because they do not affect protein

conformation. A possible exception is reported for g-irra-

diation, which affected the allergenic potential [51, 52],

depending on the dose. This may be due to chemical

changes occurring in the proteins, perhaps via free radical

reactions. Molecular separation techniques such as ultra-

filtration could, in principle, be used to remove allergens,

but in actual practice this will not be easy. Such an operation

will change the properties of a food, and not all food

matrices lend themselves to such an operation.

A completely different approach is to develop and select

plant varieties via breeding that are containing a reduced

content of major allergens. This has been investigated for

wheat in relation to celiac disease [53] and for apples [54]. In

combination with food-processing operations, such an

approach can lead to foods that can be eaten by people who

would normally be allergic for such foods.

Recently, it has been found that the molecular behaviour

of recombinant allergens can be quite different from aller-

gens isolated from their natural environment [55]. This is of

importance, because many studies are actually performed

with recombinant allergens and it is thus not straightfor-

ward to translate such results to foods.

3.2 Secondary plant metabolites

Secondary plant metabolites comprise compounds such as

carotenoids, polyphenols and glucosinolates. They have

received much attention as non-nutrients in the last decade

because of their putative role of health-promoting capacity

in relation to consumption of fruits and vegetables. There is

quite some discussion whether or not it is beneficial to eat

fruits and vegetables raw or processed. There seems to be a

common understanding among the public that fresh fruits

and vegetables are to be preferred over processed ones. The

question is whether this image is supported by scientific

research. Indeed, processing does have an effect. Macera-

tion, heating and various separation steps can result in

oxidation, thermal degradation, leaching and other events

that lead to lower levels of food components in processed

food compared with fresh food [56]. However, below we

present results that show that there are also positive bene-

ficial effects of processing.

3.2.1 Carotenoids

Carotenoids appear generally to be affected by processing

such that bioavailability is improved, especially when

destructive factors (e.g. oxygen, light and heat) are kept to a

minimum [57]. Carotenoids are hydrophobic compounds

present in plant leaves in chloroplasts as lipoprotein

complexes and, in the case of carrot root and tomato fruit, in

chromoplasts where they are deposited in crystalline form

[58]. Heat treatment is able to disrupt the molecular linkages

between carotenoids and proteins. For instance, it has been

reported that boiling of fresh broccoli promotes the release

of b-carotene from the matrix due to denaturation of caro-

tenoproteins, leading to better extractability and higher

concentrations in cooked samples [59, 60]. Similarly, boiling

of fresh carrots resulted in a slight increase of 14% of

b-carotene content compared with the raw ones [60].

The role of heating for carotenoid bioavailability has been

reported in human dietary intervention studies. In a human

cross-over study, the daily consumption of processed carrots

and spinach over a 4-wk period produced a plasma b-caro-

tene response that averaged three times that associated with

the consumption of the same amount of b-carotene from

these vegetables in the raw form [61]. This finding was

recently confirmed in a human intervention study, demon-

strating that the rate of b-carotene absorbed from a single

portion of cooked carrots is significantly higher (two-tailed

t-test) than the rate values obtained by ileostomy volunteers

Table 3. Effects of processing on the presence/absence (formation/destruction) of potentially harmful compounds

Compounds Food product Process Effect Reference

3-MCPD Soy sauce Acid hydrolysis, heating Increase [213, 214]Diterpenes Coffee Filtration Decrease [215]Trans fatty acid Spreads Transesterification Decrease [216, 217]Trans fatty acid Spreads Hydrogenation Increase [218]Furan Coffee, baby foods Stirring Decrease [219]Acrylamide Potato, cereals, coffee Frying, roasting at low water activity Increase [37]Polyaromatic hydrocarbons Meat Barbecueing, grilling Increase [167]Heterocyclic amines Meat Roasting, frying Increase [167]

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1225


eating raw carrot meals (p 5 0.048). The absorption of an

oral dose of 15 mg b-carotene provided in a raw carrot meal

was 41.477.4%, whereas absorption of b-carotene from a

cooked carrot meal reached 65.177.4% [62]. Similarly, the

bioavailability of lycopene, of which the major dietary

sources are tomato and tomato products, has been shown to

be much higher from processed tomato products (e.g.tomato paste) as compared with fresh tomato in human

dietary intervention studies both after acute and after

chronic consumption [63, 64]. However, different results

were obtained after the administration of a test meal

containing fresh or domestic cooked cherry tomatoes in

human [65]. Among the reasons discussed by the authors to

explain the lack of significant changes in carotenoid plasma

concentrations in volunteers, the short cooking period (only

15 min) was mentioned.

The influence of food matrix on carotenoid bioavailability is

not the same among carotenoids. Indeed, the relative bioa-

vailability of lutein from spinach is greater than that of

b-carotene (i.e. 67 and 14%, respectively) and less affected by

the food matrix [66]. This emerged from a human dietary

intervention study where differently processed spinach

products were investigated. It was observed that the bioavail-

ability of lutein from spinach was higher than that of

b-carotene and that enzymatic disruption of the matrix

(cell-wall structure) enhanced the bioavailability of b-carotene

from whole leaf and minced spinach, but had no effect on

lutein bioavailability [66]. The release of lutein into an aqueous

environment is probably higher than that of b-carotene

because of its lower lipophilicity compared with b-carotene [67].

In addition to light and the presence of triplet sensitizers

(e.g. chlorophyll), heat treatment also promotes the isomer-

ization of carotenoids in foods, from trans to cis isomeric

forms, and the degree of isomerization is directly correlated

with the intensity and duration of heat processing [61]. Fresh

sweet potatoes, carrots and tomatoes contain negligible

quantities of cis-b-carotene. However, after canning, the

proportion in these vegetables was found to be substantially

increased [68]. Usually, cis-isomers are less stable and have

lower melting points than their all-trans counterparts, due to

a decreased tendency to crystallization [69]. Moreover, 13-cis-b-carotene and 9-cis-b-carotene possess lower relative provi-

tamin A capacity than all-trans-b-carotene (53 and 38%,

respectively). Apart from reduced provitamin A activities,

trans-cis isomerization also affects bioavailability and anti-

oxidant capacity of carotenoids. Several human studies indi-

cate that in the case of b-carotene, the all-trans-isomer is

absorbed preferentially to the cis-isomers [69].

Experimental results indicate that, in contrast to b-caro-

tene, lycopene remained relatively resistant to heat-induced

geometrical conversion during typical food processing of

tomatoes and related products [70]. Nevertheless, serum and

tissue lycopene consist of between 50 and 90% cis-lycopene

isomers. This observation has led to the hypothesis that cis-

isomers of lycopene are produced during food processing,

cooking or digestion and are more bioavailable [71]. The

improved absorption of lycopene cis-isomers is hypothe-

sized to result from greater solubility in mixed micelles, a

lower tendency to aggregate and the shorter length allowing

the molecules to ‘‘fit’’ into micelles with greater ease [72].

This hypothesis has been recently confirmed in a human

dietary intervention study in which a significant increase in

lycopene absorption was observed when tomato sauce was

enriched in cis-isomers by heat treatment [73]. The addi-

tional heat treatment of the tomato matrix, enhancing

availability of lycopene to digestive and absorptive processes,

could also have contributed to this result. However, the

results further suggest that preferred absorption of cis-

lycopene isomers alone cannot explain the dramatically

increased proportion of lycopene cis-isomers in biological

samples upon heating, an observation that probably reflects

an additional in vivo isomerization from all-trans- to cis-

isomers. The authors conclude that, based on these find-

ings, tomato-based food products could be manipulated by

temperature processing to favour the formation of specific

isomer patterns to improve lycopene bioavailability and

possibly health benefits.

In addition, the key role of heat treatments in the caro-

tenoid bioavailability emerges indirectly from a recent cross-

sectional study in which vitamin A and carotenoids status

and related food sources were evaluated in raw food diet

adherents in Germany [74]. Fruit and vegetable consump-

tion by raw food diet adherents was higher (approximately

1800 g/day, mainly fruits) than the average consumption of

the general population in the USA (391 g/day) [75] or the

recommended fruit and vegetable consumption (400–800

g/day) [76]. The raw food diet adherents showed normal

vitamin A status and achieved favourable plasma b-carotene

concentrations as recommended for chronic disease

prevention. However, despite the high intake of plant foods,

they showed low-plasma lycopene levels, demonstrating that

processing is an important factor in determining lycopene

plasma concentration.

3.2.2 Glucosinolates

Glucosinolates occur in Brassica vegetables and these

compounds are considered to be health promoting because

of the isothiocyanates derived from them [77]. The latter are

potent inducers of Nrf2, a transcription factor involved in

the cell protection against oxidative stress. Isothiocyanates

need to be cleaved from their glucosinolate precursors to

exert activity [77–79]. This is mediated by the plant-derived

enzyme myrosinase that is sequestered in myrosin cells in

the intact plant. Only upon injury of the plant during

harvesting, food preparation and mastication, the myrosi-

nase comes into contact with the glucosinolates to liberate

the active compounds. Verkerk and Dekker [77] give an

extensive review of the fate of glucosinolates in the food

chain, including the effect of industrial as well as home

cooking processing. Glucosinolates themselves are affected



by heat [80], as well as the enzyme myrosinase. Myrosinase

is inactivated by heating but is also present in gut micro-

biota [81]. Thus, for glucosinolates to be converted/cleaved

into active isothiocyanates the plant cells need to be

damaged to liberate myrosinase. Some studies demon-

strated that among cooking methods steaming entails an

increase of glucosinolates present in broccoli probably due

to the disintegration of plant tissue upon heat that favours

the release of these compounds from the cell walls [60, 82].

On the contrary, glucosinolates, which are water-soluble

compounds, are usually lost during conventional cooking

methods (e.g. boiling) because of leaching into surrounding

water. In that respect, microwaving may be a better alter-

native because of the absence of cooking water [77]. Dekker

et al. [83] and Dekker and Verkerk [84] have presented

mathematical models to predict the fate of glucosinolates-

over the food chain, including processing. They also discuss

the consequences of a food chain approach for epidemiolo-

gical studies on the role of phytochemicals.

3.2.3 Polyphenols

Among phytochemicals present in plant foods, polyphenols

are a huge group of secondary metabolites of plants and are

generally involved in defence against oxidative stress,

ultraviolet radiation or aggression by pathogens. These

compounds may be classified into different groups as a

function of the number of phenol rings that they contain

and of the structural elements that bind these rings to one

another. Distinctions are thus made among the phenolic

acids, flavonoids, stilbenes and lignans. In addition to this

diversity, polyphenols may be associated with various

carbohydrates and organic acids [85] and they are generally

dissolved in vacuoles and the apoplast of plant cells [56].

Polyphenols are highly reactive compounds and good

substrates for various enzymes, including poly-

phenoloxidases, peroxidases, glycosidases and esterases.

They undergo numerous enzymatic and chemical reactions

during post-harvest food storage and processing. Although

the occurrence of such reactions and their roles in the

development or degradation of food quality is well docu-

mented, the structures of the resulting products are still

poorly understood and few studies are available on the

effects of thermal treatment on these compounds as well as

on their bioavailability in cooked foods.

The consequences of food processing on the fate of

polyphenols may differ greatly in relation to their concen-

tration, chemical structure, oxidation state, localization in

the cell, possible interactions with other food components

and type of thermal processing applied. Food processing

may be responsible for a decrease, increase or minor

changes in content and in functionality of polyphenols.

Zhang and Hamauzu [86] observed a loss of phenolic

compounds for boiled and microwaved broccoli, and similar

results were reported by Sahlin et al. [87] for fried tomatoes

and by Ismail et al. [88] for blanched and boiled spinach. The

cooking of vegetables, causing softening and breaking of

cell-wall components with subsequent release of the mole-

cules, determines the extent of leaching of water-soluble

polyphenols into the surrounding water during water-

cooking methods (e.g. boiling) or may destroy polyphenols

by high temperature as in the case of frying. However,

different cooking methods may differently affect the content

of polyphenols. Applying three domestic cooking methods

(i.e. boiling, steaming and frying), it has recently been

demonstrated that for carrots, zucchinis and broccoli, there

was a significant decrease in phenolic acids and flavonoids

in boiled and fried vegetables, whereas steaming preserves

polyphenols [60]. Similar results were obtained on four

vegetables belonging to the cruciferous vegetable family

cooked by steaming, microwaving and boiling: steamed

vegetables showed the highest total phenolic value, follow-

ing by boiled and microwaved ones [89].

On the contrary, the content and the functionality of

some phenolic compounds might also increase during

heating. Some studies described the influence of thermal

treatments on the conversion of caffeoylquinic acids into

other isomers. Recently, Takenaka et al. [90] found an

increase of 3-caffeoylquinic, 4-caffeoylquinic, 3,4-di-

caffeoylquinic and 4,5-di-caffeoylquinic acids on boiled

sweet potatoes due to the isomerization of 5-caffeoylquinic

and 3,5-di-caffeoylquinic acids, the major phenolic

compounds of this vegetable. The authors hypothesized that

heat is one of the factors causing the isomerization. When

the plant is heated, the cell and organelles can sustain

damage, causing phenolic compounds and poly-

phenoloxidase to meet and react, and parts of the phenolic

compounds are isomerized. Thus, the behaviour of phenolic

compounds during cooking of the sweet potato is influenced

by heat; they can react with the enzyme until the enzyme is

inactivated by temperature. A significant increase (ranging

from 66 to 94%, depending on the cooking method applied)

in total caffeoylquinic acids was also observed in artichoke

after boiling, steaming and frying procedures [91]. This

enhancement of polyphenolic content was the result of both

isomerization and hydrolysis events, leading to a substantial

re-distribution of phenolic acid concentrations. This beha-

viour determined a consistent increase of 5-O-caffeoylquinic

and 1,5-di-O-caffeoylquinic acids, particularly in steamed

and fried samples, and of 3,5- and 4,5-di-O-caffeoylquinic

acids, the concentration of which is very low in the raw

product and strongly enhanced during processing. Accord-

ingly, Slanina et al. [92] observed an increased caffeoylquinic

acids isomer content in the leaves of Cynara cardunculus L.

(artichoke thistle) caused by the intramolecular trans-ester-

ification of 5-O-caffeoylquinic and 1,5-di-O-caffeoylquinic

acids promoted by the high temperatures. Higher poly-

phenol content in blanched artichokes compared with raw

samples was also reported [93, 94].

Beside isomerization and intramolecular trans-esterifica-

tion, chlorogenic acid (CGA) can undergo hydrolysis during

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1227


heating, resulting in a consequent increase in caffeic acid.

This effect has recently been observed during domestic

heating (e.g. steaming and frying) of carrots in which a

significant increase in caffeic acid content was reported [60].

As far as polyphenol bioavailability is concerned, it is well

known that polyphenols are poorly adsorbed, highly meta-

bolized or rapidly eliminated [85]. Whether heat processing

can affect the bioavailability of polyphenols is not yet known.

To our knowledge, the only study that explored the effect of

processing on the polyphenolic bioavailability is that of

Bugianesi et al. [65], who carried out a human cross-over

study to evaluate the effect of domestic cooking on the bio-

availability of antioxidants (i.e. carotenoids and polyphenols)

after the administration of a test meal containing cherry

tomatoes. The results demonstrated that plasma concentra-

tions of naringenin and CGA increased significantly with

respect to baseline (po0.05) after administration of cooked

cherry tomatoes, but not after administration of raw cherry

tomatoes. Naringenin is trapped in the cutin matrix of the

membrane of the ripe fruit where it strongly interacts with

insoluble polyesters that are constituents of tomato fibre. As

stated by the authors, the mechanical and heat treatments

may provide the energy necessary to break the interactions,

improving naringenin bioaccessibility in vivo. In a recent

study of the same group [95], an indirect role of domestic

cooking on the bioavailability of artichoke polyphenols was

demonstrated. Indeed, in steamed artichoke heads, the

content of mono- and di-caffeoylquinic acids was higher than

in the uncooked vegetable. The consumption of cooked arti-

choke in humans resulted in a significant increase in plasma

levels of hydrocinnamic acids (i.e. CGA, caffeic, ferulic,

dihydrocaffeic and dihydroferulic acids), demonstrating for

the first time the bioavailability of metabolites of these acids.

3.2.4 Total antioxidant activity

Along with changes in the content of bioactive compounds,

some authors showed that various heat treatments are able

to increase the total antioxidant capacity (TAC) of vegetables.

The antioxidant activity of a compound can either be a

radical scavenging activity based on single electron transfer

or be a hydrogen abstraction reaction, or based on

the induction of cell-signalling pathways that lead to the

induction of Nrf-2. The TAC is an index that describes the

ability of antioxidants present in food to scavenge preformed

free radicals. The TAC depends on the synergistic and redox

interactions between the different molecules present in the

food [96]. Obviously, different cooking methods have

different effects on TAC. In a recent study exploring the

effect of domestic cooking methods on TAC of 17 vege-

tables, boiling generally resulted in positive TAC changes, a

general negative effect was observed with pan-fried vege-

tables, whereas deep frying produced an increase in TAC of

potato, artichoke and aubergine, but a TAC reduction of

mushroom and onion [97].

Miglio et al. [60] reported an overall increase in TAC

values of all cooked vegetables (i.e. carrots, zucchinis and

broccoli). In particular, in the case of carrots and zucchinis,

frying resulted in the highest TAC increase, followed by

boiling and steaming, whereas steamed broccoli showed the

highest TAC values compared with vegetable cooked by

other methods. Similarly, steaming led to an increase in

antioxidant capacity of four vegetables belonging to the

cruciferous vegetable family: the effect was modest for

cabbage (13%), but in cauliflower, broccoli and choy-sum

the TAC values more than doubled after 5 min of steaming,

compared with the uncooked vegetable [89]. The positive

effect of steaming was observed also in the case of artichoke;

indeed, this cooking method resulted in the highest TAC

increase of artichoke compared with the other two methods

(i.e. boiling and frying) [91]. In two studies, Dewanto et al.[98, 99] demonstrated that thermal processing was able to

enhance the nutritional value of tomatoes, by increasing the

bioaccessible lycopene content and the TAC values, and of

sweet corn by 44%, despite the loss of vitamin C. Accord-

ingly, Turkmen et al. [100] stated that moderate heat treat-

ment might be considered a useful tool in improving health

properties of some vegetables since they observed an

increase in TAC of pepper, green beans, broccoli and

spinach during cooking procedures (i.e. boiling, steaming

and microwaving).

The observed increase in TAC values in cooked vegetables,

extremely high in some cases [91], cannot be merely attrib-

uted to a release of antioxidant compounds from the plant

matrix. The trans-cis isomerization of carotenoids, the intra-

molecular trans-esterification of polyphenols as well as their

polymerization, leading to the formation of compounds

which are not yet identified but probably showing very high

antioxidant activity, promoted by high temperatures cannot

be ruled out. Moreover, the antioxidant properties of poly-

phenols may change with respect to their oxidation state. In

fact, although enzymatic and chemical oxidations of poly-

phenols are generally responsible for a decrease in their

antioxidant properties, recent findings have suggested that

partially oxidized polyphenols can exhibit higher antioxidant

activity than the corresponding non-oxidized forms [101].

This was attributed to the increased ability of partially

oxidized polyphenols to donate a hydrogen atom from the

aromatic hydroxyl group to a free unpaired electron. More-

over, during heating, the increases of TAC values might be

due to the formation of MRPs that possess antioxidant

activity (see the following section).

3.3 Bioactive effects of processed foods due to the

MRPs

The Maillard reaction is the prime example of a processing-

related reaction with large consequences. Many reviews on

the Maillard reaction are available and the chemistry will not

be discussed here. Rather, we focus on metabolic effects.



The first metabolic transit data of fructoselysine as an

Amadori compound in human volunteers have been

reported by Erbersdobler et al. [102], showing that urinary

excretion of orally administered fructoselysine is about 3%

and fecal excretion about 1%. These data confirmed a

hypothesis made 16 years before [103], when the intestinal

microflora was thought to degrade Amadori products. This

hypothesis was finally proven by Wiame et al. [104] who

discovered the enzyme fructoseamine-6-kinase, which

enables Eschericha coli and other species to metabolize

Amadori products.

In the past 20 years, a few more studies focused on the

metabolism of food-derived MRPs (for review, see [105–108]),

all demonstrating an absorption rate of low-molecular-weight

MRPs of up to 30%, depending on the structure and the

administered dose. Bergmann et al. [106] used positron

emission tomography to monitor biodistribution and elim-

ination of radiofluorinated carboxymethyllysine (CML), a

compound formed in the Mailllard reaction. The authors

found that the compound was rapidly absorbed, transported

into circulation and rapidly excreted through the kidneys.

For high molecular weight melanoidins, [107, 108]

reported a urinary excretion rate of a 10 000 Da fraction of a14C-labeled, at 1001C heated casein/glucose mixture of 4.3%,

as opposed to a 27% urinary excretion of the administered

dose for the low-molecular-weight fraction of less than

10 000 Da. Taken together, there is considerable evidence

that low- and even high-molecular MPRs are being absorbed

at least to some extent, albeit metabolic transit data for an

MRP structure showing an antioxidant activity in vivo are

still lacking. For heat-treated foods, however, numerous

intervention trials in animals and humans have been

performed aiming at increasing the antioxidant capacity in

plasma or tissues.

Numerous publications report on the antioxidant capacity

of MRPs. In most cases, either MRPs prepared by heating

reducing sugars with amino acids or proteins, or heat-treated

foods, such as e.g. coffee, were tested for their antioxidant

activity in cell-free systems (in situ), in cell-based assays

(in vitro), or in animal-feeding studies or human intervention

trials (in vivo). Also, a few ex vivo experiments where blood,

namely LDL isolated thereof, from healthy volunteers was

treated with MRPs are reported.

Results from cell culture experiments in which heat-

treated foods, food-derived MRPs or heated MRP model

mixtures of reducing sugars and amino acids/proteins or

isolated compounds thereof are tested for their antioxidant

activity cannot always be transferred to in vivo situations,

especially when pharmacokinetic data are missing. Cell-free

in situ tests might have some merit as indicators for the

food’s oxidative stability and shelf-life.

The formation of MRPs with antioxidant activities in

model reactions between reducing sugars and amino acids

in situ has been demonstrated in [109] who analysed model

browning reactions between the reducing sugars glucose or

fructose and cysteine or glutathione. The radical scavenging

activity measured as Trolox equivalents increased after heat

treatment, although model mixtures heated for 4 h 20 min

showed higher Trolox values than those heated for 14 h and

no correlation to browning was found. For the glucose/

cysteine model mixture, the antioxidant activity was also

demonstrated in a bacterial-based assay in hydrogen perox-

ide exposed salmonella. In this experiment, treatment with

the glucose/cysteine mixture heated at 1031C for 14 h

prevented hydrogen peroxide-induced mutations. This

result was demonstrated only without metabolic activation.

When, in the same experimental setting, salmonella were

pre-incubated with a metabolic activation system using liver

microsomes, treatment of hydrogen peroxide exposed

salmonella with model mixtures heated for shorter times

such as 4 h 20 min resulted in increased mutations, indi-

cating a pro-oxidative effect. These results clearly demon-

strate an antioxidant effect of MRPs formed from the

reaction of glucose and cysteine in situ. The fact that meta-

bolic activation by liver microsomes ex vivo abolished this

effect indicates that an antioxidant activity measured in situand, depending on the reaction conditions, also in vitromight not be transferable to in vivo situations.

Dittrich et al. [110] analyzed MRPs from model reactions

for their capacity to prevent copper-induced oxidation of

LDLs isolated from human volunteers. MRPs were gener-

ated by heating glucose with glycine, lysine or arginine. All

of the heated mixtures were more or less equally effective as

ascorbic acid in preventing LDL oxidation. Two individual

amino reductone compounds, supposed to be formed by the

Maillard reaction from glucose, were also tested for their

antioxidant capacity and were found to be less effective than

ascorbic acid at equimolar concentrations. However, the

question whether these two compounds were the active

principles in the heated glucose/amino acid mixtures was

not answered since the formation of these two compounds

was not shown.

The most recent evidence that food-derived MRPs elicit

antioxidative properties in human has been reported by

Dittrich et al. [111]. The authors administered diets poor and

rich in MRPs to eight healthy volunteers in a weekly turn for

3 wk. The diet rich in MRPs contained dark beer, bread crust

and roasted coffee and led to a statistically significant

increased oxidative stability by 35.5% of isolated LDL against

copper-induced oxidation. Although the experimental

design of this study does not allow to draw conclusions

about the active principles, the fact that administration of

severely heat treated foods versus mildly heat treated foods

resulted in an increased oxidative stability of LDL strongly

supports the hypothesis that dietary MRPs exhibit anti-

oxidant properties in vivo.

Coffee is one of the most commonly studied foods for the

formation of MRPs and their biological effects, probably due

to the intense heat treatment of the raw coffee beans during

roasting and its widespread consumption. Given the fact

that most of the naturally present phenolic antioxidants are

degraded during roasting, the overall antioxidant activity of

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1229


roasted coffee is mainly attributed to high-molecular-weight

MRPs, i.e. the melanoidins [112, 113]. Anese and Nicoli [114]

studied the influence of some technological variables on the

changes of the antioxidant capacity of ready-to-drink coffee

brews and demonstrated a higher redox potential for brews

prepared from dark roasted versus medium and light roasted

coffee beans. When coffee beans are roasted with the addi-

tion of sugar (so-called torrefacto roasting), the antioxidant

activity is even higher than that of conventionally roasted

coffees, probably due to increased formation of MRPs [115].

Next to the roasting conditions, Lopez-Galilea et al. [115]

demonstrated that also the brewing procedure, by applying

different temperatures, hydrostatic pressures and using

different ratios of coffee powder to water, has an impact

on the antioxidant activity of the coffee brews: Espresso

coffees showed the highest antioxidant activity, measured by

2,2-diphenyl-1-picrylhydrazyl radical scavenging activity,

over mocha, plunger (french press) and filtered coffee.

When coffee brews were administered to human volun-

teers, the TAC of the plasma increased shortly after

consumption. Natella et al. [116] reported a statistically

significant 7% increase in the antioxidant capacity of plasma

samples taken from healthy volunteers 2 h after intake of

200 mL regular coffee beverage. These results are in accor-

dance with those reported by Esposito et al. [117], demon-

strating an increase of the main water-soluble antioxidant in

the plasma, glutathione, after administration of five cups of

regular coffee per day to healthy volunteers for 1 wk.

CGA undergoes numerous transformations in vivo,

resulting in the formation of derivatives that might be not as

effective as the parent compound [118]. Trigonelline is

degraded into N-methylpyridinium during roasting [119],

leading to relatively low concentrations in the coffee bever-

age. Interestingly, strong antioxidant effects of N-methyl-

pyridinium and a lyophilized de-caffeinated coffee brew

have been described by Somoza et al. [120] following a 10-

day administration to rats. In both experimental groups,

plasma TAC and also a-tocopherol concentrations were

significantly increased compared with non-treated controls.

Next to N-methylpyridinium, there might be other coffee-

derived antioxidants yet not identified, e.g. melanoidins

[121]. Although melanoidins comprise high-molecular-

weight compounds, unlikely to be absorbed to exert

antioxidant activities in vivo, these compounds might be

degraded upon intestinal digestion, resulting in absorbable

structures with antioxidant effects. Rufian-Henares and

Morales [122] reported that low-molecular-weight

compounds released by gastrointestinal digestion from a

coffee melanoidin fraction with a molecular weight >10 kDa

exerted high antioxidant activities, even higher than those

compounds bound to melanoidins by ionic interaction.

Thus, gastrointestinal digestion is able to modify coffee

melanoidins to some extent, either by modifying/releasing

the ionic interaction with melanoidins and/or by the

generation of new structures from the melanoidin skeleton

after enzymatic treatment.

Coffee surrogates are often made of barley that also

contains MRPs after roasting. Papetti et al. [123] compared

effects of fractionated water extracts prepared from roasted

and natural barley for their antioxidant activity by means of

the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay

and the inhibition of linoleic acid peroxidation in hepatic

microsomes of rats. The highest antioxidant activity was

attributed to a MW fraction between 1000 and 2000 kDa of

roasted barley. Based on the elemental composition, the

authors hypothesized that the active compound was a

polysaccharide-containing melanoidin.

Beer is also rich in MRPs and melanoidins due to the

malting and brewing process. The antioxidant properties of

beer were reported to correlate both with the level of total

polyphenols and with the content of melanoidins. Rivero et al.[124] studied the antioxidant capacity of blond, dark and

alcohol-free lager beers, showing that the oxidative damage of

calf thymus DNA resulting in the formation of 8-OH-dG after

induction by copper/ascorbic acid was prevented by co-incu-

bation with the various beers, of which the darkest beer was

most effective. When malt (5% w/w) was fed to rats for 15

days, plasma contents of tocopherol increased by 14%,

whereas the levels of thiobarbituric acid reactive substances

were decreased [125]. In this study, the antioxidant effect of

malt was demonstrated in vivo for the first time. Further

investigations by Somoza et al. revealed that one of the key

antioxidants in malt is pronyl-lysine, earlier identified as the

most effective antioxidant formed in bread crust by means of

cell culture experiments and an animal feeding trial [126].

Main systemic effects of dietary malt, bread crust and pronyl-

BSA were demonstrated to be enhanced antioxidant capacity

and increased expression of chemopreventive enzymes.

Cocoa, like coffee, is thermally processed and contains

MRPs as well as numerous bioactive flavonoids, such as

epicatechin. A recent study on potential beneficial effects of

cocoa melanoidins could not identify significant antioxidant,

antimutagenic or pro-mutagenic activity [127]. No effects,

neither pro- nor antioxidant, were observed with water-solu-

ble fractions of green and roasted cocoa in Salmonella strains

TA100 and TA98, with or without metabolic activation using

liver microsomes. A weak indication for a pro-oxidative effect

in Salmonella strain TA102 was observed with the 5–10 kDa

MW fraction of roasted cocoa at the highest concentration

tested (10%), the only sample that reached statistical signifi-

cance. The highest antioxidant scavenging activity was found

in the 10–30 kDa fraction of roasted cocoa. All other MW

fractions (o5, 5–10, 10–30, >30 kDa) prepared from non-

roasted and roasted cocoa showed similar curves for growth

inhibition of bacterial strains (E.coli, Enterobacter cloacae,Bifidobacteriaum Bb-12 and B 7.1), with some inhibition at the

highest concentration tested (100mg/mL). In contrast to these

results from in vitro experiments, Jalil et al. [128] performed

an animal study on the effects of cocoa extract which was

given to obese-diabetic rats in a dose of 600 mg/kg body

weight for 4 wk. The results indicated that plasma contents of

8-isoprostane as oxidative stress biomarker were significantly



(po0.05) reduced, whereas the catalytic activity of the anti-

oxidant enzyme superoxide dismutase was significantly

enhanced after cocoa supplementation. These results are in

line with those reported by Ramiro-Puig et al. [129] who also

showed an increased superoxide dismutase activity and anti-

oxidant capacity in plasma and tissues following natural

cocoa supplementation (4 or 10% food intake) in weaned rats

for 3 wk. However, whether the in vivo antioxidant effects of

cocoa are caused by flavonoids or MRPs has to be identified

in future studies.

4 Evaluation of potential health benefits

4.1 General considerations concerning

epidemiological studies

Depending on the type of epidemiological study (cross-

sectional or prospective cohort studies, randomized

controlled trials), different issues need to be taken into

consideration. A great concern and reason for conflicting

outcomes of epidemiological studies in humans is related to

confounding factors. For instance, coffee drinking is part of

an individual’s lifestyle and can be directly linked to other

lifestyle factors that may influence the outcome, such as

alcohol intake, smoking, stress, sedentary lifestyle/lack of

physical activity and dietary habits. Heavy coffee drinking is

also associated with lower socioeconomic status. On the

other hand, people may have switched to decaffeinated

coffee or avoid coffee because of the perception that caffei-

nated coffee is part of an unhealthy lifestyle [130–132].

Misclassification of food intake can occur depending on the

methods used for assessment, variability in portion size but

also due to the variability of food components depending on

the type of processing and preparation.

Polymorphisms in the metabolism of food constituents

may play an important role, as well as dietary habits or

medication that potentially influence the activity of enzymes

involved in the metabolism of food components (or viceversa). Reverse causation is another factor to be taken into

account. For instance, an association may be identified

between low coffee intake and increased blood pressure.

Other than a causal relationship (low coffee intake causes

high blood pressure) it is likely that a person who knows

about its high blood pressure or another health problem

avoids or reduces coffee intake [130–132].

Epidemiological studies available to date mostly deal with

specific foods, nutrients, micronutrients or even contami-

nants present in the diet and their association with human

health (e.g. whole grain, red meat and aflatoxin). Little

information is available on how people cook foods before

eating. Therefore, specific information on process-related

changes and their effects on human health is rarely

addressed in food intake assessments, mainly because these

changes are difficult to quantify. No information on

processing is generally available on some food items, for

instance breakfast cereals, potatoes and bread, epidemiolo-

gical evidence for which will not be discussed in this review.

In the following sections, we discuss the epidemiological

evidence related to coffee, cocoa, beer and tomato, for which

some information related to processing is available, as

shown in the previous section. It is known that nutritional

quality of such food items is strongly affected by processing.

The roasting process of coffee and cocoa strongly affects

which compounds are going into the cup: in fact, many

compounds are formed, modified, destroyed or remain

unchanged upon roasting [133]. Dark-coloured beers (e.g.dark and stout) are produced from dark-coloured malts that

have been kilned for a longer period and at a higher

temperature than lager/pilsner malt. In dark-coloured beers,

the kilning process of malt produces compounds that make

them different from the lager beers.

As already discussed in the previous section, the bio-

availability of protective compounds in tomato is strongly

affected by processing. In the majority of epidemiological

studies on health effect of tomato, relative risks for the

combined intake of raw and cooked tomato products are

reported. However, in few of them information about

processing is included in the analysis. The effect of

uncooked tomato should be described separately from that

of cooked tomato, making tomato a perfect case for

considering the effect of processing on chronic disease risks.

4.2 Coffee

Epidemiological studies addressing the health effects of coffee

were originally initiated due to the presumed adverse effects.

Coffee consumption was associated with increased risk

factors for cardiovascular disease (CVD) including increased

blood pressure, blood cholesterol and plasma homocysteine.

There is some evidence that risk factors such as serum

cholesterol (total and LDL cholesterol) can be increased by

coffee consumption. The effect is strongly depending on the

type of brew, being associated with boiled, non-filtered coffee

that contains significant amounts of the coffee diterpenes

cafestol and kahweol [134, 135]. The increase of blood

homocysteine through coffee intake has also been discussed

as a risk factor for coronary heart disease; however, epide-

miological study results are inconclusive [132, 136].

However, more and more recent epidemiological studies

did not confirm some of the presumed health risks, on the

contrary, some seem to indicate even beneficial effects [137].

There is good epidemiological evidence that regular intake of

coffee may decrease the risk for type 2 diabetes [132, 138].

Most epidemiological studies on the association between high

coffee intake and various diseases such as coronary heart

disease (arrhythmia, stroke and infarction), cancer or bone

health revealed conflicting results, often depending on the

type of study used (case control or prospective cohort studies),

with the majority showing no association after correction for

various confounding factors like smoking [131, 136, 137].

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1231


Recommendations to limit coffee intake are maintained

today, for special risk groups, like pregnant women or

women of childbearing age, children and older adults,

whereas for normal subjects, mounting evidence indicate

possible beneficial effects of coffee consumption.

4.3 Bioactive compounds in coffee that may affect

human health

Caffeine is a natural alkaloid found in coffee beans, tea leaves,

cocoa beans and other plants. Of these, coffee has the highest

content, with varying amounts in the final beverage depend-

ing on the type of preparation of the coffee brew. For instance,

brewed coffee was reported to contain 72–130 mg of caffeine

in one cup in the US, whereas the amount in espresso was

lower ranging from 58 to 76 mg in one cup [139].

The diterpenes cafestol and kahweol are reported to be

responsible for the increase in serum total and LDL

cholesterol levels. Observational studies have indicated that

the type of preparation of the brew may influence the

concentration of the diterpenes in coffee. An association

between coffee intake and increased serum cholesterol

levels was most evident in Scandinavian countries, where

coffee was brewed preferably by boiling, whereas an asso-

ciation was less evident in countries where filtered coffee

was preferred. The diterpenes, which are present in coffee

oil, are extracted to the brew, but were found to be trapped

when filtering through paper filters [131].

CGAs are a family of esters between quinic acid and

trans-cinnamic acid (caffeic acid), which are an important

group of dietary polyphenols. Coffee is a rich source of

these dietary antioxidants. Roasting affects the CGA

composition and also generates some derivatives with

potential beneficial activity [140]. Coffee is the most impor-

tant source of CGAs in the human diet. Part of the CGAs is

absorbed in the human gastrointestinal tract and metabo-

lized in the body and part of it reaches the colon, where

CGAs are metabolized by the gastrointestinal microflora.

The antioxidant capacities of CGAs are well established

in vitro; however, due to their extensive metabolism, the

biological and antioxidant effects in humans at usual dietary

intakes remain to be established [141].

4.4 Potential beneficial effects of coffee

consumption

4.4.1 Type 2 diabetes mellitus

Several epidemiological studies have found an inverse

association between coffee consumption and type 2 diabetes.

The association seems to be consistent between different

populations and after adjustment for various confounders.

Furthermore, a dose dependency was established with a

greater reduction of the risk with higher consumption

across gender. Consumption of four or more cups of coffee

was generally associated with a significantly reduced risk,

with more variable results for lower levels of consumption.

There are indications that this holds true also for decaffei-

nated coffee, but not for tea, indicating that components

other than caffeine are responsible for the effect. These

associations seem to be supported by experimental studies

in animals and humans relating coffee consumption to

beneficial effects on insulin sensitivity, glucose homeostasis

and the blood glucose response. On the contrary, in short-

term metabolic studies, caffeine intake was shown to

increase insulin sensitivity and to exaggerate the blood

glucose response to glucose loads, which was hypothesized

to be related to the antagonistic effects of caffeine on the

adenosine receptor. Some beneficial effects are discussed of

decaffeinated over caffeinated coffee, regarding postprandial

glucose response, fasting plasma insulin concentrations

and insulin sensitivity. However, based on the available

evidence, long-term consumption of caffeinated coffee

appears to decrease rather than increase the risk for type 2

diabetes [132].

4.4.2 Prevention of Parkinson’s disease

Both case control and prospective cohort studies have

found inverse associations between coffee and caffeine

intake and Parkinson’s disease in men. In women, the

association was initially not evident, but it turned out that an

association was found in women not taking postmenopausal

hormone replacement therapy, whereas an association

was absent in women undergoing this therapy. The asso-

ciation was also present with caffeine intake from sources

other than coffee. One study even found an increased risk

for Parkinson’s disease from high coffee intake (46 cups)

in women under hormone replacement therapy. As a

possible mechanism, the co-localization in the brain of

adenosine receptors that are restricted to the striatum, the

target receptors of caffeine and the target of the dopami-

nergic neurons that degenerate in Parkinson’s disease is

discussed. Animal studies suggested that blocking of

adenosine receptors reduced chemically induced dopami-

nergic neurotoxicity in an animal model of Parkinson’s

disease [131].

4.4.3 Cancer

The strongest epidemiological evidence relating coffee and

reducing risk of cancer pertains to colorectal and liver

cancers [142].

4.4.3.1 Colorectal cancer

An inverse association between the coffee consumption

and the risk of colorectal cancer has been found in

several case–control studies, but an association was not



consistent in prospective cohort studies. A recent

meta-analysis, including 12 prospective cohort studies

from the US, Europe and Japan showed no significant effect

of coffee consumption on colorectal cancer risk.

However, an indication of an inverse association was found

in women (consuming 44 cups/day) that was slightly

stronger when controlled for the confounding factors

smoking and alcohol, and in studies with shorter follow-up

time [143].

4.4.3.2 Hepatic injury, cirrhosis and hepatocellularcarcinoma

Chronic liver inflammation can result in cirrhosis, and

progressive formation of fibrotic scar tissue may eventually

result in hepatocellular carcinoma. The most common

causes for cirrhosis in developing countries are alcohol

abuse and viral hepatitis B and C infection. A number of

cross-sectional studies have found an inverse association

between coffee intake and serum g-glutamyl-transferase, a

marker for hepatic injury and alcohol intake. An inverse

association was also identified for alanine aminotransferase,

a marker for hepatic injury. However, a reversed causality

was put forward to explain this effect; since people experi-

encing adverse effects after drinking coffee due to liver

injury might abstain from drinking coffee (caffeine meta-

bolism is inhibited in cirrhotic liver resulting in adverse

effects). In one study, the association persisted when

correcting for this possibility. The risk of liver cirrhosis was

consistently inversely correlated with the consumption of

two or more cups of coffee in several case control and

prospective cohort studies. This was also observed for

hepatocellular carcinoma and for heavy alcohol

drinkers [144], whereas the strongest inverse association was

found in people infected with hepatitis C virus. The

mechanism by which coffee prevents hepatocarcinoma is

not well established, but the induction of phase II liver

detoxification enzymes and increased glutathione levels

by the coffee diterpenes cafestol and kahweol is discussed

[131].

4.4.3.3 Stroke

A recent study reports an inverse association between coffee

consumption and stroke in women [145]. After adjustment

for factors such as age, smoking, menopausal status,

hormone replacement therapy, physical activity, alcohol

intake, aspirin use and dietary factors, the association

persisted. This was also the case for further adjustment for

high blood pressure, hypercholesterolemia and type 2

diabetes. Decaffeinated coffee intake also showed a trend

towards lower stroke risk.

4.5 Processed barley

Processed barley is employed to prepare coffee substitutes

and to produce beers. Up to date, epidemiological and

interventional studies have not addressed the health effects

of barley coffee, whereas more information is available on

beer consumption. Unfortunately, most of the studies

on beer did not consider the type of beer (lager, sprout,

dark etc.). As a consequence data, interpretation was mainly

addressed on the effect of alcohol and in some cases

discussion was focused on the polyphenols moiety mainly to

explain the differences observed between wine and beer.

After wine intake was suggested as a possible explanation

for the lower than expected CHD mortality rates in France

(the French Paradox), many studies have dealt with the

question of whether different alcoholic beverages are

equivalent in their ability to protect against CHD or whether

a specific beverage might offer a greater protection.

Evidence obtained from a meta-analysis of 26 observational

studies [146] indicates an average significant reduction of 32

and 22% of overall vascular risk associated with drinking

wine and beer, respectively.

Regarding the effect of beer in human intervention

studies, controversial results have been obtained. Imhof

et al. [147] evaluated the effect of different alcoholic

beverages (red wine, beer and ethanol and the same

beverages de-alcoholized) on ex vivo migration of mono-

cytes, which represents a crucial step in early athero-

sclerosis, in a human open randomized intervention study

over 3 wk. Results demonstrated a statistically significant

inhibitory effect after ethanol and de-alcoholized red wine

consumption, but no effect for consumption of beer, de-

alcoholized beer and red wine. However, in a randomized

controlled crossover trial performed recently by the same

group [148], an increase of adiponectin concentration was

observed among women after consuming red wine (29.8%,

po0.05), whereas this was different among men after

ethanol solution (17.4%, po0.05) and consuming beer

(16.1%, po0.05). The authors concluded that moderate

amounts of ethanol-containing beverages increased adipo-

nectin concentrations, but sex-specific effects might depend

on the type of beverage consumed. An influence of gender

on the effect of beer consumption was reported also by a

Spanish group. In several human intervention longitudinal

studies carried out by these researchers, moderate

consumption of beer during a month was associated, espe-

cially in women, with favourable changes on the blood lipid

profile (i.e. increase of HDL-cholesterol, erythrocytes,

haematocrit and mean corpuscular volume) [149], on para-

meters describing the non-specific immunity (i.e. increase of

white blood cell counts and phagocytic and oxidative burst

activity) [150] and on the immune function (i.e. increase of

CD31 cells only in women, increase of IgG, IgM and IgA

concentrations, IL-2, IL-4, IL-10 and IFN-g cytokine

production in both gender) [150].

Components produced during the kilning process at

higher temperatures may be responsible for the higher invitro anti-mutagenic activity of dark-coloured beer against a

variety of mutagens, including heterocyclic amines, than

that of pilsner-type beer [151]. However, single-cell gel

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1233


electrophoresis assay (comet assay) revealed that oral

ingestion of pilsner-type and stout beers for 1 wk signifi-

cantly inhibited DNA damage in the liver cells of male mice

exposed to 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline,

a heterocyclic amine. This demonstrates that anti-mutagenic

effects of two beers in vivo were approximately the same,

although the anti-mutagenic effect of the dark-coloured

beers was stronger than that of pilsner-type beers in the

in vitro experiments. This inconsistency may be caused by

the difference in bioavailability of active components from

both types of beer, as stated by the authors [151]. Similarly,

at the high dose (1/2-diluted beer) both lager and dark beer

significantly inhibited atherosclerosis compared with a

control of 2% alcohol when these beverages were provided

for 10 w to cholesterol-fed hamsters, an animal model of

atherosclerosis [152]. Moreover, lager significantly decreased

cholesterol and triglycerides, and both beers acted as in vivoantioxidants by decreasing the oxidizability of LDLs.

4.6 Tomatoes

In the past years, a large body of epidemiological studies has

explored the relationship between the intake of tomato and

tomato-based products on cancer risk. Based on the most

extensive review of the epidemiological literature published

by Giovannucci [153] 10 years ago, the intake of tomatoes

and tomato-based products was consistently associated with

a lower risk of a variety of cancers. Evidence was strongest

for cancers of the lung, stomach and prostate gland and is

suggestive for cancers of the cervix, breast, oral cavity,

pancreas, colorectum and esophagus. More recently, the US

Food and Drug Administration (FDA) received a petition for

qualified health claims regarding tomatoes and the risk

reduction of some forms of cancer [154]. Based on FDA’s

review of the strength of the total body of publicly available

scientific evidence for the consumption of tomatoes or

tomato-based food and reduced risk of cancer, the agency

found that there was very limited evidence to support an

association between tomato consumption and reduced risks

of prostate, ovarian, gastric and pancreatic cancers. The

reasons for such judgement, in disagreement with the

observational evidence mentioned above, are due to: (i)

mixed results found in case–control, case–cohort and

ecologic studies evaluated in the case of prostate cancer; (ii)

very limited credible evidence for other cancer sites. More-

over, the FDA found no credible evidence for an association

between tomato consumption and a reduced risk of lung,

colorectal, breast, cervical or endometrial cancer.

The majority of studies reported relative risks for the

combined intake of raw and cooked tomato products. Only a

few studies reported relative risks for raw tomatoes and

cooked tomato products separately, suggesting stronger

protective effects of cooked tomatoes than for raw tomatoes.

Bosetti et al. [155] conducted a case–control study in Greece

with 320 cases of prostate cancer and 246 controls. The

intake of both raw and cooked tomatoes was inversely

associated with prostate cancer risk, but the relationship for

cooked tomatoes was stronger than for raw ones (odds ratios

for the lowest versus the highest tertile of intake 5 1.91, 95%

confidence interval (CI) 5 1.20–3.04 for cooked tomato

and 5 1.55, 95% CI 5 1.00–2.52 for raw tomato). In a

prospective cohort study, Giovannucci et al. [156] followed

47 365 men for approximately 12 years, during which 2481

cases of prostate cancer were identified. Among all the

tomato sources measured, consuming one or more than one

serving of tomato sauce per week was associated with a

statistically significant decreased incidence of prostate

cancer (RR 5 0.80, 95% CI 5 0.70–0.91). Tomato sauce

intake was evaluated with the use of a 131 items food–

frequency questionnaire that was administered at the

beginning of the study and at 4-year intervals thereafter.

These results confirmed an earlier reported association

between tomato sauce and a reduced risk of prostate cancer

in the same cohort [157]. A protective effect of tomato sauce

was also observed in a case–control study in which the

association between tomato and tomato-based food intakes

and the risk of ovarian cancer among 549 case patients and

516 control subjects from the United States was explored

[158]. This study found that those who ate tomato sauce two

or more times per week had a statistically significantly lower

risk of ovarian cancer (OR 5 0.60, 95% CI 5 0.37–0.99),

whereas no association was found between intake of raw

tomato and the risk of ovarian cancer (OR 5 0.88, 95%

CI 5 0.50–1.54).

Less explored is the relationship between the risks of

CVD and type 2 diabetes mellitus (DM) and the consump-

tion of tomato and tomato-based products. In a cohort of

middle-aged and older women from the United States, the

RR of CVD for those consuming tomatoes or tomato juice

suggested no clear association with either CVD or important

vascular events [159]. Conversely, comparing women

consuming Z2 servings/wk versus no tomato sauce, the age-

and treatment-adjusted RR of total CVD was 0.66 (p for

linear trend 5 0.008). Different results were obtained in the

same cohort when the intake of tomato and tomato-based

products was explored in relationship with the risk of DM

[160]. On average, women consumed a total of 4.3373.22

servings of tomato-based food products per week, of which

2.18 were from tomatoes, 1.14 from tomato sauce, 0.57 from

pizza and 0.44 from tomato juice. Women who consumed

greater amounts of tomato-based food products had neither

a significantly decreased nor a increased risk of type 2 DM

and the associations for individual tomato-based food

products were similar to the results for the combination of

all tomato products.

The stronger inverse associations seen for tomato sauce

compared with other sources of tomatoes are probably

linked to, as argued by Giovannucci [161], the higher bio-

availability of lycopene after heat treatment and the addi-

tional presence of oil, which facilitates its absorption into

the intestinal mucosal cell. Although tomato juice is high in



lycopene, the absorbed amount will vary dramatically,

depending on how it is processed and whether it is

consumed alone or with a meal containing lipids.

5 Mechanistic evidence for benefitsrelated to compounds formed duringfood thermal processing

The studies on the biological effects of compounds specifi-

cally formed during processing were traditionally focused on

the potential harmful effects, as they are considered some-

how artificial. However, the evidence of the beneficial effects

exerted by some processed foods, such as coffee, promoted

the studies aimed at investigating the mechanisms and the

compounds responsible for the beneficial effects. Some

small molecular weight compounds such as pronyl-lysine

and N-methylpiridinium, as well as some quinide

compounds derived from CGAs have been identified.

Recently, the structures of two classes of food melanoidins

such as those present in coffee [113, 162–165] and in bread

crust [126] were elucidated allowing to shed some light on

the possible biological activities of these compounds.

Table 4 summarizes an overview. In the following section,

the available evidence is grouped according to the biological

effects.

5.1 Effects on liver detoxification enzymes

5.1.1 Functioning of the liver detoxification system

To understand the effect of compounds on the liver detox-

ification system, it is useful to have an overview of the

functioning of this complex system. Detoxification enzymes

generally function to minimize the potential of damage

from xenobiotics living organisms are exposed to, such as

pharmaceuticals, environmental or food components. Many

of these compounds show little relationship to previously

encountered compounds or metabolites and most of them

are of non-polar structures, which do not allow urinary

excretion. In order to prevent xenobiotics from being accu-

mulated in tissues, a complex system of detoxifying

enzymes has evolved to transform these compounds into

polar, water-soluble structures that can be easily excreted

through the urine.

Literature suggests considerable evidence for an associa-

tion between impaired detoxification and the risk for various

diseases, such as some types of cancer [166–168], Parkin-

son’s disease [169] or chronic immune dysfunction

syndrome [170]. On the other hand, the intake of fruits and

vegetables containing compounds that induce detoxification

enzymes, such as antioxidants, has been shown to lower the

risk for, e.g. colorectal cancer [171].

The biotransformation of xenobiotics occurs in two

phases: functionalization, which uses oxygen to form a

reactive site, and conjugation, which results in addition of a

water-soluble group to the reactive site. These two steps,

functionalization and conjugation, are termed Phase I and

Phase II detoxification, respectively. The result is the

biotransformation of a lipophilic compound into a water-

soluble compound to be excreted in urine (Fig. 3).

The Phase I detoxification system, composed mainly of

the cytochrome P450 supergene family of enzymes, is

generally the first enzymatic defense against xenobiotic

compounds. Most pharmaceuticals are metabolized through

Phase I biotransformation. In a typical Phase I reaction, a

cytochrome P450 enzyme uses oxygen and, as a cofactor,

NADH, to add a reactive group, such as a hydroxyl radical.

As a consequence of this step in detoxification, sometimes

highly reactive molecules, which may be more toxic than the

parent molecule, are produced. If these reactive molecules

are not further metabolized by Phase II conjugation, they

may cause damage to proteins, RNA and DNA within the

cell. Several types of conjugation reactions are present in the

body, including glucuronidation, sulfation, and glutathione

and amino acid conjugation. These reactions require

conjugating compounds such as glucuronic acid, sulfate,

glycine, glutamine, taurine, ornithine or glutathione. Anti-

oxidants exert health beneficial effects by scavenging reac-

tive Phase I intermediates (see previous section) or by

inducing Phase II enzymes.

A Phase III detoxification system is currently under

discussion, referring to transmembrane transporter/anti-

porter activity (p-glycoprotein or multi-drug resistance

proteins). Such membrane transporter activity is an impor-

tant factor in the first pass metabolism of pharmaceuticals

and other xenobiotics. The antiporter is an energy-depen-

dent efflux pump, which pumps xenobiotics out of a cell,

thereby decreasing the intracellular concentration of xeno-

biotics [172]. Since antiporter activity in the intestine

appears to be co-regulated with intestinal Phase I Cyp3A4

enzyme [173], antiporter proteins may support and promote

detoxification. Possibly, their function of transporting non-

metabolized xenobiotics out of the cell and back into the

intestinal lumen may allow more opportunities for Phase I

activity to metabolize the xenobiotic before it is taken into

circulation. However, Phase I and Phase II enzyme proteins

are highly expressed in the liver and the kidneys, whereas

enterocytes show some but not highest expression levels.

5.1.2 Modulation of liver detoxification enzymes by

thermally treated foods

Heat treated-foods and even MRP structures formed therein

have been demonstrated to modulate Phase I and Phase II

enzymes in animal-feeding trials. Kitts et al. [174] first

reported decreased Phase I aryl hydrocarbon hydroxylase

activity in small intestinal enterocytes of mice which were

fed an experimental diet containing 2% MRPs for 10 wk.

MRPs were prepared by heating an equimolar mixture of

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1235


glucose and L-lysine at 1211C for 4 h. Pintauro and Lucchina

[175] administered a heat-treated protein, egg albumin, to

rats for 10 wk and also demonstrated a decreased activity

of the Phase I enzyme aminopyrine N-demethylase in

small intestinal enterocytes, whereas hepatic Phase I

benzo[alpha]pyrene hydroxylase activity was significantly

increased. Although both feeding trials from Kitts et al. [174]

and Pintauro and Luccina [175] clearly indicated an effect of

MRPs on detoxifying enzymes, the active principles were

still unknown. Wenzel et al. [176] administered heat treated

casein that was selectively fortified with the MRP Ne-CML.

After a feeding period of 10 days, Phase II glutathione

S-transferase (GST) activity in rat colonic enterocytes and

kidneys increased by 64 and 86%, respectively, compared

with control animals on a standard diet containing equiva-

lent amounts of non-heated casein. However, the heat-

treated casein did not only contain CML and other MRPs

might have contributed to this Phase II enhancing effect.

When CML as a purified, non-protein-linked compound was

tested for its GST-modulating activity in Caco-2 cells, a

statistically significant decrease of 10% was observed after

the cell’s treatment with 0.5 mM CML for 48 h [105]. Thus,

CML is unlikely to be a potent inducer of Phase II GST

activity. In order to clarify whether the Phase I/II modu-

lating activity is more affected by high- or by low-molecular-

weight compounds, Faist et al. [105] tested various mela-

noidin fractions of different molecular weight prepared

from hot water extracts of roasted caraffa malt in Caco-2 cell

cultures. The low-molecular-weight fraction of o10 000 Da

was most effective in activating Phase I NADPH-cyto-

chrome c reductase and Phase II GST activity (1122 and

133% versus control, respectively). The majority of the mid-

molecular-weight compounds tested showed an activating

effect on Phase I NADPH-cytochrome c reductase and an

inhibitory effect on GST activity. These effects were most

pronounced for compounds of up to 70 000 and

4200 000 Da, but less distinct for fractions of an average

molecular weight of 100 000 Da.

Lindenmeier et al. [125] first identified an MRP structure

with strong Phase I and Phase II modulating activities that

was formed in bread crust upon heat treatment. In accordance

with the well accepted fact of antioxidants being potent

inducers of Phase II enzymes through cellular binding to the

‘‘antioxidant responsive element’’, this compound was also

characterized as the key antioxidant in bread crust. Briefly,

application of an in situ antioxidant assay to solvent fractions

isolated from bread crust revealed the highest antioxidative

potential for dark brown, ethanol soluble compounds. Both

bread crust and, in particular, the intensely brown, ethanolic

crust fraction induced a significantly elevated Phase II GST

activity and a decreased Phase I NADPH-cytochrome

c reductase activity. Antioxidant screening of Maillard-type

model mixtures, followed by structure determination revealed

a pyrrolinone reductonyl-lysine, abbreviated as pronyl-lysine,

of which high concentrations were quantified in the bread

crust (62.2 mg/kg), whereas low concentrations were analyzed

in the crumb (8.0 mg/kg). Exposing Caco-2 cells for 48 h to

either synthetically pronylated albumin or to purified pronyl-

glycine significantly increased Phase II GST activity by 12 or

34%, respectively, thus demonstrating for the first time that

‘‘pronylated’’ proteins as part of bread crust melanoidins act as

monofunctional inducers of GST, serving as a functional

parameter of an antioxidant, chemopreventive activity in vitro.

Next to bread crust and malt, coffee brews were also

studied for their effects on Phase II enzymes [125]. In this

study, N-methylpyridinium iodide was identified as the key

compound modulating Phase II GST. In vivo effects of a

decaffeinated coffee beverage and N-methylpyridinium iodide

Table 4. Beneficial effect of melanoidins and food components rich in food melanoidins

Compounds Study design Measure Outcome Reference

Bread crust Animal Liver enzyme activity Enhanced antioxidant capacity increaseschemopreventive enzymes

[126]

Bread crust In vitro Gutmodel

Growth of bacteriaspecies

Prebiotic activity [220]

Bread crust In vitro tests ACE and MIC Anti-ACE activity antibacterial activity [186]Fractionated melanoidins

Roasted maltCultured cells

(Caco2)Enzyme activity Activation CCR and the GST [221]

Coffee Silverskin In vitro Gutmodel



Various coffee melanoidins In vitro system Prevention of dentaldiseases

Inhibition of adhesionBinding of Streptococcus mutansto tooth enamel

[223]

Coffee melanoidins, beer ACE inhibitory [122]Coffee melanoidins In vitro Gut

modelGrowth of bacteria

speciesPrebiotic activity [188]

Coffee melanoidins In vitro Gutmodel



Coffee melanoidins In vitro Gutmodel





were tested in a 15-day animal trial on rats. As a result,

feeding of 4.5% coffee beverage resulted in an increase of

Phase II GST and UDP-glucuronyl-transferase activity by 24

and 40%, respectively, compared with animals fed the control

diet. Animals on the N-methylpyridinium diet showed an

increase in liver Phase II UDP-glucuronyl-transferase of

65% compared with controls. The mechanism by which

N-methylpyridinium ions induce Phase II enzymes was

recently identified by Bottler et al. [177] who showed that this

compound effectively induced the gene transcription and

translocation of Nrf2, a major transcription factor leading to

the expression of antioxidant and Phase II enzymes, such as

GST. These results are in line with findings reported by Cavin

et al. [178] who demonstrated an induction of Nrf2-mediated

cellular defence and alteration of detoxifying enzyme activities

as mechanisms of chemoprotective effects of coffee in the

liver of rats. However, controlled intervention trials are still

needed to verify the contribution of N-methylpyridium ions

and potential other health beneficial compounds in coffee to

the reduced risk for diseases such as various types of cancer

which are associated with an endogenous load of reactive

oxygen species and decreased activities of detoxification

enzymes.

5.2 Experimental and mechanistic studies on anti-

cancer activity

The potential anticarcinogenic activity of food compounds is

usually assessed by inhibitory activity on the growth of

human tumor cells, mutagenicity tests as well as by inves-

tigating the effect on DNA oxidation and on the mitogen-

activated protein kinase cascade. Traditionally, compounds

formed upon thermal treatment were mainly considered for

their potential carcinogenic activity (i.e. acrylamide or

heterocyclic amines). However, there are some in vitrostudies performed with the chemically characterized Mail-

lard-type chromophores formed under mild heating condi-

tions. These compounds were shown to be potent inhibitors

of the growth of human tumor cells in the low micromolar

range, causing tumor cell cycle arrest and apoptosis induc-

tion. This effect is due to their ability to suppress the

induction of the mitogen-activated protein kinase cascade,

one of the major signalling pathways in the regulation of

cell growth [179]. Antimutagenic properties of MRP or

melanoidin mixtures have been noted by Kim et al. [180] and

were attributed to the inhibition of mutagen absorption or to

the inhibition of mutagen activation [181].

Oxidative stress and subsequent DNA damage can be

considered as potential biomarkers to investigate the

mechanisms of the potential anticancer activity of whole

foods. As far as coffee and liver cancer is concerned,

Bichler et al. [182] reported a protection of human lym-

phocytes against DNA damage induced. Blood samples

were taken from human volunteers who consumed

600 mL of regular coffee per day for 5 days and lympho-

cytes were cultivated in the presence of H2O2 or Trp-P-2

assessing DNA damage by the comet assay (single-cell

gel electrophoresis). DNA damage was significantly reduced

after coffee consumption, as compared with the induced

damage before the intervention. Analysis of the cytosolic

enzymes of the lymphocytes after coffee consumption

showed an increased activity of superoxide dismutase

(138%), whereas glutathione peroxidase remained

unchanged.

Similar results were obtained in a human intervention

study showing protection against DNA damage induced by

the polycyclic aromatic hydrocarbon BPDE (anti-benzo-

[a]pyrene-dihydrodiol-epoxide) in isolated peripheral

lymphocytes after coffee consumption [183]. Experiments

comparing paper filtered versus non-filtered coffee further-

more indicated that this effect cannot be ascribed to the well-

known bioactive coffee diterpenes cafestol and kahweol.

5.3 Antimicrobial and antibacterial activity

The first study showing the inhibitory mechanism of anti-

bacterial MRPs was run by Einarsson [184] using the

Salmonella mutagenic test system. They showed that the

IntermediaryXenobioticsmetabolites

Excretoryderivatives

Phase I reactions

Cytochrome P450 enzymes

Phase II reactions

Conjugation pathways(e.g. Glutathions S transferase)Non polar,

lipid solubleMore polar,

less lipid solublePolar,

water soluble

Reactive oxygenintermediates

Oxidative damageof organic molecules

Antioxidants

induction

inhibition

Bile Serum

Feces Urine

Reactive oxygenintermediates

Figure 3. Liver detoxification

pathways and their interac-

tion with antioxidants.

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1237


MRPs tested had no mutagenic effect and that their anti-

bacterial effect was primarily due to the interaction between

MRPs and iron, resulting in reduced oxygen uptake.

Recently, Rufian-Henares and de la Cueva [185] tested the

ability of coffee melanoidins against the growth of different

pathogenic bacteria. They found that at low concentrations

melanoidins exerted a bacteriostatic activity mediated by

iron chelation from the culture medium, whereas at high

concentrations they exerted a bactericidal activity by

removing Mg21 cations from the outer membrane,

promoting the disruption of the cell membrane and allow-

ing the release of intracellular molecules. Also different

molecular weight fractions isolated from roasted cocoa have

been tested for their antibacterial effects [127]. All fractions

reduced the growth of pathogenic bacteria; however, the

authors highlighted that the growth of Bifidobacteria was

also inhibited.

Hiramoto et al. [186] determined the inhibitory activity of

a variety of melanoidins on urease-gastric mucin adhesion.

Extracellular urease proteins located on the surface of Heli-cobacter pylori are gastric mucin-targeted adhesins, which

play an important role in infection and colonization to the

host. In addition, they have determined the anti-colonization

effect of melanoidins prepared by heating casein and

lactose, in an animal model and in human subjects infected

with this bacterium. They concluded that melanoidins

might be an alternative to antibiotic-based therapy to prevent

H. pylori growth that combines safety, ease of administra-

tion and efficacy.

The high-molecular-weight material obtained by an

enzymatic extraction procedure from bread crust inhibited

the growth of Escherichia coli ATCC 25922 and Staphlococcusaureus ATCC 25923 [187]. Data demonstrated that the more

severe the thermal treatment the higher the antibacterial

activity, suggesting that melanoidins play an important role.

5.4 Prebiotic activity

Prebiotics are non-digestible food ingredients that stimulate

the growth or activity of bacteria in the digestive system,

which are beneficial to the health of the body. Usually, this

term refers to soluble dietary fibre (fructo-oligosaccharides

and inulin) that is able to increase the concentration of

lactobacillus and bifidobacteria. Actually also food melanoi-

dins, as part of food indigestible material that reach the

lower gut and can be metabolized by the gut microflora,

should be considered as potential prebiotic material. This

concept was first investigated by Ames et al. [188]. They used

glycated BSA as a test substance and no prebiotic activity

was found. Borrelli et al. [112] demonstrated that the high-

molecular-weight fraction enzymatically extracted from

bread crust increased the growth of Bifidobacteria and a

similar effect could be observed using the coffee silverskin, a

by-product of coffee roasting very rich in coffee melanoidins

[113].

Recently, a series of articles [162, 189, 190] showed that

the high-molecular-weight fraction from coffee brew

contains three fractions that can be distinguished into

galactomannans, arabinogalactans and melanoidins. The

chemical characteristics of these fractions depended not

only on the roasting conditions, but also on the coffee

preparation procedure. They demonstrated that coffee

melanoidins behave as a soluble dietary fibre since they are

fermented by the gut microflora. High amounts of acetate

and propionate were produced after microbial degradation

of high-molecular-weight components from coffee.

It can be hypothesized that polysaccharide-rich melanoi-

dins such as those present in coffee are preferentially

metabolized by Bifidobacteria, whereas protein-rich mela-

noidins, as obtained by protein glucose mixtures or milk-like

systems, are good substrates for protein metabolizing

bacteria predominantly present in the descending tract of

the colon.

5.5 Anti-ACE activity

Two articles have addressed the possibility that MRPs

influence the activity of angiotensin-I converting enzyme.

This enzyme, whose activity plays a key role in the increase

of blood pressure, is inhibited by various food-derived

peptides, which are candidates for the management of blood

pressure. Del Castillo et al. [187] showed that the natural

ACE inhibitory activity of wheat gluten was reduced by

thermal treatment as a consequence of the reaction with

sugars. On the other hand, Rufian-Henares and Morales

[122] found that melanoidins isolated from beer and coffee

were able to inhibit ACE and that the efficacy of coffee

melanoidins increases with roasting degree.

5.6 Effect on type 2 diabetes

Results reported by Natella et al. [116], Esposito et al. [117],

Bichler et al. [182] and Steinkellner et al. [183] clearly show

that drinking of coffee enhances the antioxidant capacity of

human plasma and isolated cells thereof. Subclinical

inflammation, imparting enhanced oxidative stress to the

organism, has been considered to be a risk factor for type 2

DM and its complications. However, it is still not clear

whether and to what extent antioxidative effectiveness might

contribute to the evidence that moderate coffee consump-

tion (three to four cups per day) is associated with decreased

risks for certain diseases, including DM type 2 [191,

192–194], colon cancer [195], liver cirrhosis [144], Alzhei-

mer’s disease [196] and Parkinson’s disease [197].

Although for all of these diseases, the endogenous load of

reactive oxygen species is increased compared with healthy

subjects, controlled intervention trials to prove this hypo-

thesis are mostly lacking. Very recently, results of a human

trial published by van Dijk et al. [198] demonstrated that the



intake of two major coffee components, CGA (1 g) and

trigonelline (500 mg) significantly reduced glucose and

insulin concentrations in the plasma of healthy volunteers

15 min, following an oral glucose tolerance test compared

with placebo. Since reactive oxygen species are hypothesized

to play a pivotal role in the progression of DM [199], the

reduced risk for this disease following regular coffee

consumption might be at least in part caused by its contents

of CGA and trigonelline, although these two compounds

might not be the only or most effective antioxidants ingested

with a moderate coffee consumption of two to three cups perday in vivo.

Further evidence for beneficial effects on type-2 diabetes

also comes from a Canadian group focusing on the role of

CGA derivatives [140]. Roasting transforms CGA into

quinides that can alter blood glucose levels acting through

gut peptides (glucose-dependent insulinotropic polypeptide

and glucagon-like peptide-1). Shearer et al. [200] demon-

strated that 3,4-diferuloyl-1,5-quinide increases whole-body

glucose disposal independently of skeletal muscle and that

decaffeinated coffee has a beneficial effect on glucose

management in rats [200].

6 Concluding remarks

Consumer perception of (mainly industrial) processing is

rather negative, probably due to the large attention to

formation of undesired compounds, but clearly processing

also leads to the formation of compounds with beneficial

properties. Moreover, industrial processing can be control-

led and optimized much better through the application of

kinetic principles than household cooking. It appears from

this review that many individual compounds as well as

compounds from model reactions or whole foods have been

analysed in vitro for health beneficial characteristics. The

major problem is that it is as yet not clear if these effects can

be directly interpreted as health beneficial for the consumer,

because metabolism by the gastrointestinal microflora,

bioavailability or degradation by human metabolism are of

great influence. Epidemiological data indicative of positive

effects for consumers are merely available on whole foods

but information on if and how these foods are processed is

usually not available. It is also fair to conclude that precise

mechanisms of action of individual compounds responsible

for the observed effects are less well understood.

A clear understanding of the mechanisms underlying the

biological effect is essential for obtaining the intended bene-

ficial effect in the food product. If such knowledge becomes

available, new technologies may provide new opportunities to

deliver health, quality and safety in food systems.

For the few compounds that have been isolated up to now

from processed foods, the mechanisms identified seem to

support the epidemiological data available for each specific

food. Such individual compounds are known to be formed

during the thermal processing of the whole foods.

The translation of consumer perceptions (particularly

flavour, texture and the presence of health promoting

components) into manageable industrial scale technologies

is a major challenge for the food industry and it is a

limitation of the state of the current science underpinning

modern food-processing technology. Systematic studies are

required to provide a balanced optimization for the thermal

processes that are accepted and widely used by the food

industry in terms of food safety, providing acceptable risk

and the desired benefits that are satisfactory to both to the

consumers and to the food safety risk managers (i.e. nutri-

tional and organoleptic quality, release of bioactive or

functional compounds formed during food proccessing). A

systematic application of kinetics to optimize thermal

processes to deliver benefits while ensuring safety needs to

be pursued by food technologists and food safety scientists

with urgent view to commercial implementation.

Non-thermal processes may provide less risk and equal or

even better benefits than thermal processes but are still in

their infancy and in an exploratory phase of investigation,

especially those that have potential commercial applications in

the food industry. Current non-thermal processes can, in

general, not yet offer acceptable safety alternatives compared

with thermal processes but studies are on the way, and

combinations of mild heat treatment and non-thermal

processes may give new opportunities. Also here, a systematic

application of kinetics is needed. Data on non-thermal

processes in terms of inactivation kinetics and reaction

mechanisms of nutrients, toxins, allergens, microbes and

viruses are required and shelf-life studies of non-thermally

treated products are desirable. To date, unfortunately, there

seems to be little progress in the development of industrial

application of technologies for non-thermal processes. In a

similar manner, non-thermal processes such as fermentation

can generate metabolites, giving food unique health benefits

when these processes are implemented in a controlled way.

However, new strains and substrates for release of beneficial

compounds need to be developed and the performance of

starter strains needs to be enhanced during the process.

There are rather strong indications in the scientific

literature for the effects of individual compounds that are

formed, and epidemiological data do indicate positive bene-

ficial effects of whole foods, but the evidence is not always

conclusive. The mechanisms or the compounds responsible

for effects are less well understood. Areas for further inves-

tigations include bioavailability and biotransformation of

phytochemicals in general and translation of in vitro anti-

oxidant capacity to beneficial health effects in humans.

However, there is a lack of information about the food

processing in epidemiological studies and epidemiological

studies should be designed for addressing this purpose.

Further study is required to find or synthesize pure standard

compounds to enable the conduct of more accurate

mechanistic studies and to further identify other bioactive or

functional compounds, thus providing stronger evidence of

the beneficial effects of food processing.

Mol. Nutr. Food Res. 2010, 54, 1215–1247 1239


A better understanding of the relevance of in vitro results

for human health benefits is needed, with due consideration

of intake of these compounds from foods. Databases and fit

for purpose food intake surveys to estimate the levels of

intake of these compounds are also required if the beneficial

effects of compounds derived from thermal food processing

are to be clearly established.

In conclusion, the following gaps are identified

(i) Lack of information about how foods are processed that

are considered in epidemiological studies.

(ii) Translation of antioxidant capacity in vitro to health

beneficial effects in humans.

(iii) Effects of processing on protein digestibility, notably

the effects on allergens.

(iv) Effects of non-thermal processes on phytochemicals,

melanoidins and allergens.

(v) Relevance of the in vitro results for human benefit

considering the reasonable intake of these compounds

from foods.

(vi) Lack of databases to estimate the level of intake of

compounds from processed foods.

It is the authors’ intention and hope that this review

helps in designing future study in this exciting area.

This work was commissioned by the Process-relatedCompounds Task Force of the European branch of the Interna-tional Life Sciences Institute (ILSI Europe). Industry membersof this task force are Danisco, DSM, Groupe Danone, KraftFoods, Mars, Nestle, PepsiCo International, Premier Foods,Procter & Gamble, S .udzucker/BENEO Group and Unilever.For further information about ILSI Europe, please call132-771-00-14 or email [email protected]. The opinionsexpressed herein are those of the authors and do not necessarilyrepresent the views of ILSI Europe or the ILSI Europe Process-related Compounds Task Force.

For those experts affiliated with academic institutions, ILSIEurope covered the expenses related to their participation inExpert Group meetings, and an honorarium has been provided.

The authors have declared no conflict of interest.

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